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Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs


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To evaluate the effect of high- and low-protein diets with or without tryptophan supplementation on behavior of dogs with dominance aggression, territorial aggression, and hyperactivity. Prospective crossover study. 11 dogs with dominance aggression, 11 dogs with territorial aggression, and 11 dogs with hyperactivity. In each group, 4 diets were fed for 1 weeks each in random order with a transition period of not < 3 days between each diet. Two diets had low protein content (approximately 18%), and 2 diets had high protein content (approximately 30%). Two of the diets (1 low-protein and 1 high-protein) were supplemented with tryptophan. Owners scored their dog's behavior daily by use of customized behavioral score sheets. Mean weekly values of 5 behavioral measures and serum concentrations of serotonin and tryptophan were determined at the end of each dietary period. For dominance aggression, behavioral scores were highest in dogs fed unsupplemented high-protein rations. For territorial aggression, [corrected] tryptophan-supplemented low-protein diets were associated with significantly lower behavioral scores than low-protein diets without tryptophan supplements. For dogs with dominance aggression, the addition of tryptophan to high-protein diets or change to a low-protein diet may reduce aggression. For dogs with territorial aggression, tryptophan supplementation of a low-protein diet may be helpful in reducing aggression.
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504 Scientific Reports: Original Study JAVMA, Vol 217, No. 4, August 15, 2000
The effect of food composition on the behavior of
mammals has been appreciated for many years.1,2 In
dogs, the link between dietary protein content, metab-
olism of the amino acid tryptophan, and aggressive
behavior has been the subject of considerable interest
and discussion.3Dogs fed a low-protein (LP) diet had
decreased territorial aggression in a previous study.3
Low-protein diets, in conjunction with high carbohy-
drate content, may induce their effect by changing the
plasma ratio of the amino acid L-tryptophan (Trp) to
other large neutral amino acids (LNAA), thus affect-
ing competition between Trp and LNAA for a common
blood-brain barrier transporter mechanism.4,5 Most
proteins are low in Trp and rich in LNAA so that feed-
ing a high-protein (HP) diet will reduce the Trp:LNAA,
impairing the transfer of Trp across the blood-brain
barrier.6Conversely, LP diets result in higher
Trp:LNAA, thus enhancing Trp transfer to the brain.7
Because Trp is a biosynthetic precursor for the neuro-
transmitter serotonin,8 decreased concentration of this
amino acid will lead to reduced formation of serotonin
and possibly more aggressive responses to stimuli.6,9,10
As corroboratory evidence of this hypothesis, results of
studies in humans indicate that diets low in Trp
increase aggression, anger, and depression,11,12 whereas
increased dietary Trp has a therapeutic effect in patho-
logically aggressive patients13 and promotes a feeling of
well-being in people with aggressive traits.12 In support
of the hypothesis regarding serotonin and aggression,
dogs that are dominant and aggressive have lower
mean CSF concentration of the serotonin metabolite 5-
Hydroxyindoleaceticacid (5-HIAA) than nonaggres-
sive control dogs.14
The purpose of the study reported here was to
evaluate the effect of HP and LP diets with or without
Trp supplementation on behavior of dogs with domi-
nance aggression, territorial aggression, and hyperac-
tivity. We hypothesized that LP diets and diets high in
Trp would be associated with less aggression and
reduced excitability and reactivity.
Materials and Methods
Study enrollment—Thirty-eight client-owned dogs of
various ages, breeds, and sexes were serially enrolled in the
study; 33 dogs completed the study, whereas 5 dogs did not
complete the study for various reasons. All dogs were
patients at Tufts University Veterinary School Behavior Clinic
and the study protocol was approved by the Tufts Animal
Care and Use Committee. Each dog was required to meet
specific behavioral criteria for dominance aggression, hyper-
activity, or territorial aggression (Appendices 1-3) and their
owners were required to agree to the terms and conditions of
the study and sign a consent form. Dogs were not enrolled if
they were pregnant, <5 months of age, had received psy-
choactive medication within 2 weeks of initiation of the
study, had a physical status score of <3 (on a 1-to-5 scale)15
or, because of their aggressive behavior, were an immediate
danger to people. A full medical history, physical examina-
tion, CBC, and serum biochemical analyses were performed
to screen for diseases other than behavioral abnormalities.
Study design—Dogs meeting study criteria were
Effect of dietary protein content and tryptophan
supplementation on dominance aggression,
territorial aggression, and hyperactivity in dogs
Jean S. DeNapoli, DVM; Nicholas H. Dodman, BVMS, DACVB; Louis Shuster, PhD;
William M. Rand, PhD; Kathy L. Gross, PhD
Objective—To evaluate the effect of high- and low-
protein diets with or without tryptophan supplemen-
tation on behavior of dogs with dominance aggres-
sion, territorial aggression, and hyperactivity.
Design—Prospective crossover study.
Animals—11 dogs with dominance aggression, 11
dogs with territorial aggression, and 11 dogs with
Procedure—In each group, 4 diets were fed for 1
week each in random order with a transition period of
not < 3 days between each diet. Two diets had low
protein content (approximately 18%), and 2 diets had
high protein content (approximately 30%). Two of the
diets (1 low-protein and 1 high-protein) were supple-
mented with tryptophan. Owners scored their dog’s
behavior daily by use of customized behavioral score
sheets. Mean weekly values of 5 behavioral mea-
sures and serum concentrations of serotonin and
tryptophan were determined at the end of each
dietary period.
Results—For dominance aggression, behavioral
scores were highest in dogs fed unsupplemented
high-protein rations. Tryptophan-supplemented low-
protein diets were associated with significantly lower
behavioral scores than low-protein diets without tryp-
tophan supplements.
Conclusions and Clinical Relevance—For dogs with
dominance aggression, the addition of tryptophan to
high-protein diets or change to a low-protein diet may
reduce aggression. For dogs with territorial aggres-
sion, tryptophan supplementation of a low-protein
diet may be helpful in reducing aggression. (
J Am Vet
Med Assoc
From the Department of Clinical Sciences, School of Veterinary
Medicine, Tufts University, Grafton, MA 01536 (DeNapoli,
Dodman); the Departments of Pharmacology and Experimental
Therapeutics (Shuster) and Community Health (Rand), School of
Medicine, Boston, MA 02111; and Hill’s Pet Nutrition Inc, Science
and Technology Center, PO Box 1658, Topeka, KS 66601-1658
The authors thank E. Caliguri, M. Marcos, and S. Sanchez for tech-
nical assistance.
Address correspondence to Dr. Dodman.
504_508.QXD 8/22/2005 2:40 PM Page 504
JAVMA, Vol 217, No. 4, August 15, 2000 Scientific Reports: Original Study 505
enrolled into 1 of 3 study groups, including a dominance
aggression group, a territorial aggression group, and a hyper-
activity group. For each group, 4 diets were fed for a 1-week
period each, in random order, with a transitional period of at
least 3 days between each diet. Minimum total duration of the
study for each dog was 40 days. A LP diet without supple-
mental Trp was designated LP–Trp, whereas a LP diet with
supplemental Trp was designated LP+Trp (Table 1 and 2). A
HP diet without supplemental Trp was designated HP–Trp,
whereas a HP diet with supplemental Trp was designated
HP+Trp. Because of supplementation, the Trp:LNAA was
higher in the supplemented diets, compared with the unsup-
plemented diets (LNAA concentration in the diets was not
determined). Diets met standards of the Association of
American Feed Control Officials Nutrient Profiles for Adult
Dogs and were fed to provide a daily metabolizable energy
intake of 1.6 X(70 kcal Xbody weight [kg]0.75). Thus, for a dog
that weighed 10 kg (22 lb), approximate daily Trp intake was
30, 50, 42, and 67 mg/d for LP–Trp, LP+Trp, HP–Trp, and
HP+Trp diets, respectively. Diets were coded numerically and
by a color code. Content of each diet was unknown to the
clinicians involved in the study. Owners were instructed to
feed the study diet exclusively and offer each dog 2 meals/d;
amount fed was determined on the basis of each dog’s body
weight. By use of the behavioral scores (Appendices 1-3),
owners scored their dogs daily for dominance aggression, ter-
ritorial aggression, fearfulness, hyperactivity, and excitability.
Serotonin and Trp analyses—For measurement of
serum Trp and serotonin concentrations, venous blood sam-
ples were obtained at the end of each week of the trial while
each dog was still receiving a test diet. Sampling was con-
ducted 1 to 2 hours after a meal to minimize the effect of
postprandial variations in concentration of Trp and sero-
tonin. Blood was drawn into a polyethylene syringe and
transferred to a tube containing EDTA as anticoagulant.
Samples were centrifuged for 10 minutes at 500 Xg, and plas-
ma was removed, frozen immediately, and stored at –80 C
(–112 F) for up to 2 months until time of analysis. For analy-
sis, samples were thawed and proteins were removed by cen-
trifugation for 5 minutes at 9,000 X g after addition of an
internal standard (100 µl of 10–6MN-methylserotonin) and
100 µl of 0.5Mperchloric acid to 0.5 ml of plasma. Aliquots
of the supernatant were injected into a high-performance liq-
uid chromatography apparatus equipped with either a 5-µm
carbon 18 reversed-phase columnaand a coulometric detec-
torbor a 2-µm carbon 18 reversed-phase columncand an
amperometric detector.16,17,d Concentrations of serotonin and
Trp were calculated from peak heights, relative to an internal
standard. Peak heights were adjusted relative to the internal
standard and compared with a standard curve generated on
the same day. To permit a direct comparison, serotonin and
Trp were calculated in molar amounts. All assays were car-
ried out in duplicate, and standard curves were run each day.
Statistical analyses—Mean values were determined for
results of 5 behavioral measurements that were recorded
daily by owners during each of the dietary periods. Visual
examination of the behavior data revealed that assumption of
normal distributions was appropriate. Because results of Trp
and serotonin analyses were not normally distributed, these
data were logarithmically transformed before analysis. Each
variable was analyzed independently, by use of ANOVA to
first test the effects of order of fed diets and then to test sig-
nificance of the 2 dietary factors (protein concentration,
effect of Trp supplementation) nested within experimental
groups. Interaction terms were included in the initial method
and removed if not significant. The least-significant differ-
ences method was used for post hoc analysis of differences
between behavior groups. All analyses were performed with
computer software.eDifferences were considered significant
at P<0.05.
Eleven dogs in each group completed the study;
mean ± SD age of territorial aggressive dogs was 3.7 ±
1.7 years (range, 1.5 to 8.5 years), mean age of domi-
nant aggressive dogs was 5.4 ±3.7 years (range, 2.5 to
14 years), and mean age of hyperactive dogs was 3.6 ±
2.2 years (range, 1.9 to 9.1 years).
Behavior—Significant changes in behavior were
not detected within any of the 3 groups for any of the
dietary treatments. As expected, dogs in the domi-
nance aggression group had significantly higher
dominance scores (P= 0.002) than dogs in the other
2 groups. After correcting for this factor, each behav-
ior was examined across behavioral groups for the
entire study population as a whole. By use of this
Ingredient LPTrp L PTr p HP Trp H PTrp
Corn 370 370 200 200
Poultry meal 184 184 410 410
Corn starch 156.5 155.05 295.5 294.05
Animal fat 100 100 20 20
Dried eggs 32.5 32.5 32.5 32.5
Cellulose 100 100 0 0
Natural flavora20 20 20 20
Dicalcium phosphate 15 15 0 0
Vegetable oil 10 10 10 10
Mineralsb9.4 9.4 9.4 9.4
Vitaminsc2.5 2.5 2.5 2.5
Ethoxyquin 0.1 0.1 0.1 0.1
L-Tryptophan 0 1.45 0 1.45
Values are reported as g/kg. To convert to g/lb, divide by 2.2.
aLiquid palatability enhancer. bPotassium chloride, sodium chloride, ferrous
sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, cobalt
carbonate, and sodium selenite. Mineral concentrations met or exceeded
established standards. cCholine chloride, vitamin A, vitamin D3, vitamin E,
niacin, calcium pantothenate, thiamin mononitrate, riboflavin, pyridoxine
hydrochloride, folic acid, biotin, and vitamin B12. Vitamin concentrations met
or exceeded established standards.
Table 1—Composition of experimental diets that contained low
(LP) or high (HP) concentrations of proteins and were supple-
mented with L-tryptophan (Trp) or were not supplemented
Nutrients LPTrp L PTr p HP Trp H PTrp
Protein 186 188 308 315
Fat 171 175 122 111
Crude fiber 82 73 16 14
Ash 50 50 53 54
Metabolizable energy
(kcal/kg) 3715 3789 3554 3490
Amino acids
Tryptophan 1.8 3.0 2.4 3.7
Arginine 10 10 18 18
Histidine 5 5 7 7
Isoleucine 7 7 12 12
Leucine 15 15 23 23
Lysine 9 9 14 14
Methionine 3 3 4 4
Phenylalanine 7 7 12 12
Tyrosine 3.1 3.2 5.9 6.1
Threonine 7 7 12 12
Valine 9 9 16 16
Trp:LNAA 0.04:1 0.07:1 0.04:1 0.06:1
Values are expressed as g/kg unless indicated otherwise.
LNAA Large neutral amino acids.
Table 2—Nutrient analysis of experimental diets that contained
low or high concentrations of proteins and were supplemented
with L-tryptophan or were not supplemented
504_508.QXD 8/22/2005 2:40 PM Page 505
506 Scientific Reports: Original Study JAVMA, Vol 217, No. 4, August 15, 2000
analysis, significant differences were detected
between diet groups for certain behaviors (Table 3).
Dominance scores for dogs fed the HP-Trp diet were
significantly higher than those of dogs fed the other
3 diets.
Territoriality scores among dogs in the different
behavioral groups were not significantly different.
Territoriality scores were significantly higher for dogs
fed the LP–Trp diet, compared with those fed the
LP+Trp diet.
Significant differences in fearfulness were not
detected among the 3 behavioral groups or in all dogs
among the 4 diets. Hyperactivity and excitability
responses differed (P<0.001) among the behavioral
groups; hyperactive dogs had the highest scores, domi-
nant aggressive dogs had intermediate scores, and terri-
torial aggressive dogs had the lowest scores. After cor-
recting for these differences and analyzing data from all
dogs, significant differences for hyperactivity and
excitability scores were not detected among the 4 diets.
Plasma Trp and serotonin concentrations
Significant differences were not detected among
behavioral groups or diets for plasma tryptophan or
serotonin concentrations. The natural log of the plas-
ma tryptophan concentration (nmol/ml) for the vari-
ous diets were as follows (mean ± SE): LP–Trp, 2.49 ±
0.13, LP + Trp, 2.53 ± 0.12; HP–Trp, 2.78 ± 0.12;
HP+Trp, 2.66 ± 0.12; all diets (mean ± SD), 2.61 ±
0.69. The natural log of the plasma serotonin concen-
tration (pmol/ml) for the various diets were as follows:
LP–Trp, 2.78 ± 0.18; LP+Trp, 2.59 ± 0.19; HP–Trp
2.79, ± 0.19; HP+Trp, 2.72 ± 0.18; and all diets (mean
± SD) 2.70 ± 0.90.
As a whole, results of our study supported the
hypothesis being tested. The finding that Trp supple-
mentation of the HP and LP diets of dogs with domi-
nance and territorial aggression, respectively, induced a
significant decrease in aggression scores was anticipat-
ed. Both of these Trp-supplemented diets had higher
Trp:LNAA than the 2 unsupplemented diets; the high-
er ratio may have resulted in a greater proportion of
Trp crossing the blood-brain barrier, increasing brain
serotonin concentration and decreasing aggression. A
factor that may have been operating with regard to the
HP diets is that increased dietary protein concentration
increases plasma concentrations of tyrosine and pheny-
lalanine,18 which are both catecholamine precursors;
this change could effectively reduce the threshold for
aggression.19,20 Addition of Trp (as in the HP+Trp diet)
should counter this effect by increasing brain serotonin
concentration, thus reducing aggression. Increasing
brain serotonin concentration usually decreases
aggression21,f; however, the direction of modulation of
behavior induced by serotonin varies according to the
animal’s social status.22 Furthermore, the behavior-
modifying effect induced by altering Trp concentration
depends critically on circumstance.23 Dominant ani-
mals, unlike their subordinate counterparts, may have
high, possibly fluctuating, concentrations of brain
serotonin,24 making stabilization of regional brain sero-
tonin, rather than absolute changes in its concentra-
tion, more important in terms of minimizing aggres-
Another important finding was that addition of
Trp to a LP diet reduced territoriality scores. The
LP+Trp diet had a higher Trp:LNAA that presumably
resulted in increased serotonin synthesis.25 Results of
an earlier study indicate that LP diets are associated
with a reduction in territorial-fear aggression in dogs.3
This finding was not replicated in our study.
Territoriality scores for dogs fed the LP+Trp diet were
lower than those of dogs fed either of the HP diets, but
differences were not significant.
The lack of influence of dietary protein content or
addition of Trp to the diet on the behavior of hyperac-
tive dogs was not unexpected, because results of recent
studies23,26,27 indicate no improvement in behavior of
hyperactive laboratory animals and children treated
with selective serotonin reuptake inhibitors. If potent
serotonin-enhancing strategies, like the use of selective
serotonin reuptake inhibitors, are ineffective in chang-
ing hyperactive behavior, it is unlikely that more sub-
tle measures such as dietary changes would induce an
observable effect.
Plasma concentrations of serotonin and Trp were
surprisingly consistent in all phases of our study,
despite different concentrations of dietary Trp. We had
expected that dietary differences would cause measur-
able change in the plasma concentrations of these sub-
strates; lack of such changes could indicate that the
analytic method we used was inadequate. Alternatively,
we may have missed peak plasma concentrations of
these substrates by obtaining samples 1 to 2 hours after
a meal; recent evidence indicates that peak changes in
Trp concentration may not develop until 5 hours after
a meal is fed.9Correlation between plasma serotonin
and Trp concentrations was expected, because these
Behavior LPTrp L PTr p HP Trp H PTrp
Dominance 1.12 0.17 1.29 0.17 1.84 0.17a1.04 0.18
Territoriality 3.68 0.15b3.17 0.15 3.47 0.15 3.33 0.16
Fear 2.34 0.15 2.40 0.15 2.29 0.15 2.25 0.15
Hyperactivity 3.58 0.10 3.46 0.10 3.46 0.10 3.40 0.10
Excitability 3.7 0.11 3.5 0.11 3.66 0.11 3.53 0.11
aHPTrp versus HPTrp,
0.001; HPTrp versus LPTrp,
0.024; HPTrp versus LPTrp,
0.003. bLPTrp versus LPTrp,
Table 3—Mean (SE) daily behavioral scores (corrected for group differences) for 33
dogs fed diets that contained low or high concentrations of proteins and were sup-
plemented with L-tryptophan or were not supplemented
504_508.QXD 8/22/2005 2:40 PM Page 506
JAVMA, Vol 217, No. 4, August 15, 2000 Scientific Reports: Original Study 507
are dependent variables. It may be more meaningful to
measure platelet serotonin concentration.
Results of the study reported here have potential
applications for treatment of behavioral problems in
dogs. Low-protein or Trp-rich diets may be helpful
adjuncts in the management of dominance aggression.
Also, LP diets supplemented with Trp may be benefi-
cial in reducing territorial aggression in dogs. One
caveat regarding LP diets, however, is that they should
be used only under strict nutritional guidance in
young, growing dogs (<6 months of age) and in preg-
nant and lactating bitches.
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1) Diagnosis of dominance aggression made by a behaviorist on the basis
of history and clinical findings.
2) Dogs reacted aggressively to family members in 5 of 30 dominance
aggression promoting situations3and had some aggressive behavior
at least 5 d/wk.
3) Daily dominance score ranged from 0 to 10. Criterion for a score of 1:
single episode of mild aggression (growls, lifts lip, or threatens).
Criterion for a score of 2: several episodes of mild aggression. Criterion
for a score of 3: mild aggression in many circumstances. Criterion for a
score of 4: single episode of snapping. Criterion for a score of 5: sever-
al episodes of snapping. Criterion for a score of 6: snaps in many cir-
cumstances (bites without breaking skin). Criterion for a score of 7:
bites without breaking skin in several circumstances. Criterion for a
score of 8: bites once (bruising or breaking skin). Criteria for a score of
9: bites in several circumstances (breaking skin or bruising, lunges, or
chases repeatedly), but dog can be controlled with discipline. Criteria
for a score of 10: bites (breaking skin or bruising), lunges, or chases
repeatedly in many circumstances; discipline escalates the aggression.
Appendix 1
Behavioral criteria for enrollment and assessment of dominant
aggressive dogs
1) Diagnosis of hyperactivity made by a behaviorist on the basis of histo-
ry and clinical findings.
2) Mean daily score 5 for either a hyperactivity daily assessment scale
or an excitability scale. The hyperactivity scale (range, 0 to 10) was
based on the number of hyperactive actions that were performed dur-
ing each day. The 10 hyperactive actions were excessive pacing or cir-
cling, not remaining in sit-stay or down-stay positions when required,
excessive chewing of objects or self-mutilation, being easily distracted
by extraneous stimuli, impulsive behavior (not waiting), not engaging in
any particular activity for an extended period (limited attention span),
playing roughly, barking or whining excessively, acting in an intrusive
manner, and not heeding commands. The excitability scale (range, 0 to
10) was based on assessment of the dog in 4 situations; mean values of
scores recorded during the 4 situations were used. The first situation
involved the dog's behavior at home during the daytime; a score of 0
was assigned if the dog spent most of this period asleep, whereas a
score of 10 was assigned if the dog paced and panted continuously;
scores from 1 to 9 were assigned on the basis of owner's subjective
assessment of the dog's behavior between these extremes. The sec-
ond situation was the dog's reaction to the doorbell or outside noise; a
score of 0 was assigned if the dog had no reaction, whereas a score of
10 was assigned if the dog reacted with uncontrollable excitement;
scores from 1 to 9 were assigned on the basis of owner's subjective
assessment of the dog's behavior between these extremes. The third
situation involved the dog's behavior during walks; a score of 0 was
assigned if the dog lagged behind the owner, whereas a score of 10
was assigned if the dog was uncontrollable; scores from 1 to 9 were
assigned on the basis of owner's subjective assessment of the dog's
behavior between these extremes. The fourth situation involved the
time required for the dog to resume calm behavior after stimulation; a
score of 0 was assigned if the dog became calm immediately, whereas
a score of 10 was assigned if the dog remained excited indefinitely;
scores from 1to 9 were assigned on the basis of owner's subjective
assessment of the dog's behavior between these extremes.
3) Hyperactive dogs also had to have dominance score 2.
Appendix 2
Behavioral criteria for enrollment and assessment of hyperactive
1) Diagnosis of territorial aggression was made by a behaviorist on the
basis of history and clinical findings.
2) Mean daily territorial aggression score 5. The territorial aggression
scale ranged from 0 to 10; a score of 0 was assigned if the dog did not
bark or make menacing postures or motions when strangers
approached or enter the house, whereas a score of 10 was assigned if
the dog was uncontrollably aggressive when a stranger approached the
house (barking, growling, baring teeth, charging the door, and similar
behaviors); scores from 1 to 9 were assigned on the basis of owner's
subjective assessment of the dog's behavior between these extremes.
3) Mean daily fearfulness score 3. The fearfulness scale ranged from 0
to 10; a score of 0 was assigned if the dog appeared relaxed and happy
under all circumstances, without signs of fearfulness at any time,
whereas a score of 10 was assigned if the dog had signs of extreme fear
when confronted by any strange person, situation, or experience, or if
the dog constantly followed the owner from room to room and could not
be left alone without risk of damaging itself or property.
4) Territorial aggressive dogs also had to have dominance score 2 and
hyperactive score 2.
Appendix 3
Behavioral criteria for enrollment and assessment of territorial
aggressive dogs
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508 Scientific Reports: Original Study JAVMA, Vol 217, No. 4, August 15, 2000
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plasma concentrations of basic and neutral amino acids and in red
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tein intake. Am J Clin Nutr 1984;39:722–729.
19. Haller J, Makara GB, Kruk MR. Catecholaminergic involve-
ment in the control of aggression: hormones, the peripheral sympa-
thetic, and central noradrenergic systems. Neurosci Biobehav Rev
20. Stoddard SL, Bergdall VK, Townsend DW, et al. Plasma cat-
echolamines associated with hypothalamically-elicited defense
behavior. Physiol Behav 1986;36:867–873.
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aggression. Curr Opin Neurobiol 1997;7:812–819.
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behavioral activity by norfenfluramine and related drugs in rats is not
mediated by serotonin release. Psychopharmacology 1993;111:169–178.
24. Raleigh MJ, Brammer GL, McGuire MT, et al. A dominant
social status facilitates the behavioral effects of serotonergic agonists.
Brain Res 1985;385:274–282.
25. Yokogoshi H, Wurtman RJ. Meal composition plasma
amino acid ratios: effect of various proteins or carbohydrates, and of
various protein concentrations. Metabolism 1986;35:837–842.
26. Popper CW. Antidepressants in the treatment of attention
deficit/hyperactivity disorder. J Clin Psychiatry 1997;58(suppl
27. Halpern JM, Sharma V, Siever LJ, et al. Serotonergic func-
tion in aggressive and nonaggressive boys with attention deficit
hyperactivity disorder. Am J Psychiatry 1994;151:243–248.
Correction: Effect of timing of blood collection on serum phenobarbital concentra-
tions in dogs with epilepsy
In the Results and Discussion sections of “Effect of timing of blood collection on
serum phenobarbital concentrations in dogs with epilepsy” (JAVMA, 2000;
217:200-204), the dosages were converted from mg/kg to mg/lb incorrectly.
All mg/kg dosages are stated correctly; these values should then be divided by 2.2
when converting to mg/lb. For example, in the first paragraph of the Results sec-
tion, it states, “Dosages of phenobarbital ranged from 1.0 mg/kg/d [2.2 mg/lb/d] to
10.9 mg/kg/d [24 mg/lb/d]”; this should read, “…1.0 mg/kg/d [0.45 mg/lb/d] to
10.9 mg/kg/d [4.9 mg/lb/d].”
504_508.QXD 8/22/2005 2:40 PM Page 508
... 78 Eight studies investigated predominantly dog-training, 53-55 60 72 73 76 85 with a further six studies investigating predominantly medication or diet. 56 61 66-68 80 Some studies investigated multiple interventions. In particular, legislation changes were often accompanied by education, 57 74 75 75 84 and studies on dog training methods often included medication as part of the strategy. ...
... 67 68 80 A further three studies investigated the use of medication only 56 61 66 and one with diet alone (online supplemental table 1). 56 The three studies investigating medication alone were low quality, and conclusions could not reliably be made. 56 61 66 They were limited by small sample sizes, subjective and nonstandardised owner-reported measures of aggression, and no control group. ...
... 56 The three studies investigating medication alone were low quality, and conclusions could not reliably be made. 56 61 66 They were limited by small sample sizes, subjective and nonstandardised owner-reported measures of aggression, and no control group. One used a cross-over design, however, had unreliable results with a sample size of nine. ...
Background The prevention of dog bites is an increasingly important public health topic, as the incidence of serious injury continues to rise. Objectives To evaluate the effectiveness of interventions to prevent dog bites and aggression. Methods Online databases were searched (PubMed, Cochrane Library, Embase and Google Scholar), using the search terms: dog/s, canine, canis, kuri, bite/s, bitten, aggression, attack, death, fatal, mortality, injury/ies, prevention, intervention , for studies between 1960 and 2021. All study designs were considered. Outcomes of interest were the incidence of dog bites or dog aggression. Non-English studies, and those without full-text access were excluded. Results Forty-three studies met the review criteria, including 15 observational and 27 interventional studies. Fifteen studies investigating dog-control legislation, including leash laws, stray dog control and infringements indicated this can reduce dog bite rates. Breed-specific legislation had less of an effect. Six studies investigating sterilisation, showed while this may reduce dog bites through a reduction in the dog population, the effect on dog aggression was unclear. An alcohol reduction programme showed a significant reduction in dog bite rates in one study. Seven studies assessing educational approaches found that intensive adult-directed education may be effective, with one study showing child-directed education was not effective. Eight studies on dog training (two police-dog related), and six evaluating dog medication or diet were generally low quality and inconclusive. Conclusions Multiple strategies including effective engagement with indigenous communities and organisations will be required to reduce dog-bites and other incidents involving dog aggression. This review provides some evidence that legislated dog control strategies reduce dog bite rates. Available evidence suggests greater restrictions should be made for all dogs, rather than based on breed alone. Due to a burden of child injury, protection of children should be a focus of legislation and further investigations. Prevention strategies in children require redirection away from a focus on child-directed education and future research should investigate the effectiveness of engineering barriers and reporting strategies.
... A study conducted on children by Schoenthaler and Bier [69] found that a diet rich in vitamins and minerals can reduce antisocial behavior in schoolaged children. Additionally, studies by Gesch et al. [73] confirmed these findings but also showed that supplementation with both vitamin and mineral supplements and essential fatty acids (SFA) such as docosahexaenoic acid-22: 6n-3 (DHA) reduced the occurrence of violence-related behaviors [73,74]. In the case of dogs, models of their behavior are also considered as a model for humans, and previous research indicates that diet plays an important role in the behavior of these animals [74]. ...
... Additionally, studies by Gesch et al. [73] confirmed these findings but also showed that supplementation with both vitamin and mineral supplements and essential fatty acids (SFA) such as docosahexaenoic acid-22: 6n-3 (DHA) reduced the occurrence of violence-related behaviors [73,74]. In the case of dogs, models of their behavior are also considered as a model for humans, and previous research indicates that diet plays an important role in the behavior of these animals [74]. ...
Full-text available
Aggression as a behavior is not always desirable, often ends in abandonment and/or euthanasia. However, it is possible to prevent the occurrence of unwanted aggression in domestic dogs. Aggression is not a fully understood phenomenon. In recent years, many studies have focused on the influence of diet and physiology (including the endocrine system) on the emergence of behavioral disorders. In particular, the emphasis was put on nutritional additives such as fatty acids, amino acids, and probiotics. In addition, the possibility of using neurocognition in the observation of abnormal behavior in dogs has also been discussed, which may allow for a more detailed determination of the basis of aggressive behavior in dogs. In this review, the concepts related to aggression and its potential causes have been gathered. In addition, the possible influence of diet and hormones on aggression in dogs has been discussed, as well as the application of neurocognition in the possibility of its diagnosis
... Tryptophan is the metabolic precursor to serotonin, which is a neuromodulator involved in the regulation of several behavioral processes, including aggression, mood, and stress susceptibility and -resistance in both vertebrates and invertebrates [46,47]. In fact, supplementing diet with tryptophan is widely used in domestic and livestock animals to modulate aggressiveness, hyperactivity and stress recovery [48][49][50][51]. ...
Full-text available
Background The extent and impact of evolutionary change occurring in natural populations in response to rapid anthropogenic impact is still poorly understood on the genome-wide level. Here, we explore the genetic structure, demographic history, population differentiation, and domestic introgression based on whole genome data of the endangered European wildcat in Germany, to assess potential genomic consequences of the species’ recent spread across human-dominated cultural landscapes. Results Reconstruction of demographic history and introgression rates based on 47 wildcat and 37 domestic cat genomes suggested late introgression between wild and domestic cat, coinciding with the introduction of domestic cat during the Roman period, but overall relatively low rates of hybridization and introgression from domestic cats. Main population divergence found between an eastern and central German wildcat clade was found to be of rather recent origin (200 y), and thus the likely consequence of anthropogenic persecution and resulting isolation in population refugia. We found similar effective population sizes and no substantial inbreeding across populations. Interestingly, highly differentiated genes between wild cat populations involved in the tryptophan-kynurenine-serotonin pathway were revealed, which plays a role in behavioral processes such as stress susceptibility and tolerance, suggesting that differential selection acted in the populations. Conclusions We found strong evidence for substantial recent anthropogenic impact on the genetic structure of European wildcats, including recent persecution-driven population divergence, as well as potential adaptation to human-dominate environments. In contrast, the relatively low levels of domestic introgression and inbreeding found in this study indicate a substantial level of “resistance” of this elusive species towards major anthropogenic impacts, such as the omnipresence of domestic cats as well as substantial habitat fragmentation. While those findings have strong implications for ongoing conservation strategies, we demand closer inspection of selective pressures acting on this and other wildlife species in anthropogenic environments.
... De Napoli and Dodman [31] observed an improvement in dog behavior by supplementing the dog feed with tryptophan-a serotonin precursor. In another study, Gazzano et al. [32] found that carbohydrate-based morning meals lead to significantly higher TRP/5LNAAs ratios, persistent for at least 6 h. ...
Full-text available
Serotonin is considered to be the neurotransmitter that controls several types of behavior: aggressiveness, impulsivity, food selection, stimulation, sexual behavior, reaction to pain, and emotional manifestations. The aim of this study was to determine the serotonin values in 43 dogs, divided into three different experimental variants: (1) between two groups of medium (n = 6) and small (n = 4) breed shelter dogs; (2) in dogs with (n = 15) and without (n = 10) owners after administration of pre-spaying/neutering anesthesia; (3) in different behavioral states (n = 8) classified as follows: M1—happy, M2—aggressive, M3—calmed status, post-exposure to a stressful situation, compared to the reference time referred to as M0. There were no significant differences (p ≥ 0.05) regarding the serotonin values between the two groups of medium and small breed shelter dogs. Following anesthesia, the average mean serotonin values were significantly lower (p ≤ 0.003), by 63.85 ng/mL, in stray dogs compared to dogs with owners. No significant differences (p ≥ 0.05) were found when comparing the reference time M0 to M1, M2, and M3. The differences decreased significantly (p ≤ 0.05), by 89.61 ng/mL, between M1 and M2 and increased significantly (p ≤ 0.008), by 112.78 ng/mL, between M2 and M3.
... The changes in the levels of tryptophan metabolites in response to the foods in this study is of interest in relation to prior work on the supplementation of dog food with tryptophan. In dogs with dominance or territorial aggression, dietary supplementation with tryptophan for one week reduced these aggressive behaviors [60]. Sled dogs fed supplemental tryptophan displayed a decrease in agonistic behaviors, including teeth baring, snapping, biting, and nosing [61]. ...
Full-text available
A nutrition-based approach was utilized to examine the effects of fish oil and a polyphenol blend (with or without tomato pomace) on the fecal microbiota and plasma/fecal metabolomes. Forty dogs, aged 5–14 years, were fed a washout food, then randomized to consume a control (fish oil and polyphenol blend without tomato pomace) or test (fish oil and polyphenol blend with tomato pomace) food, then the washout food, and crossed over to consume the test or control food; each for 30 days. Several metabolites differed when comparing consumption of the washout with either the control or test foods, but few changed significantly between the test and control foods. Plasma levels of 4-ethylphenyl sulfate (4-EPS), a metabolite associated with anxiety disorders, demonstrated the largest decrease between the washout food and the control/test foods. Plasma 4-EPS levels were also significantly lower after dogs ate the test food compared with the control food. Other plasma metabolites linked with anxiety disorders were decreased following consumption of the control/test foods. Significant increases in Blautia, Parabacteroides, and Odoribacter in the fecal microbiota correlated with decreases in 4-EPS when dogs ate the control/test foods. These data indicate that foods supplemented with polyphenols and omega-3 fatty acids can modulate the gut microbiota to improve the profile of anxiety-linked metabolites.
... Effects of nutrition, especially dietary amino acids and fiber, on canine behavior were discussed in a literature review (Bosch et al., 2007). Dietary protein component and tryptophan supplementation were reported to reduce canine aggression (DeNapoli et al., 2000). A nutraceutical diet could positively affect the neuroendocrine parameters in dogs with behavioral problems (Sechi et al., 2017). ...
Full-text available
Certain strains of Lactiplantibacillus were found to have a positive impact on host neuromodulation through the gut-brain axis and thus ameliorate emotional and behavioral problems. A number of researches have been performed on humans, mice and rats; however, studies on dogs are limited. Forty-five dogs with behavioral problems were enrolled in this study, including aggression (n=22), separation anxiety (n=15), compulsive disorder (n=7) and unclassifiable inappropriate behavior (n=1, excessive barking). The behavioral diagnosis was made based on the primary behavioral consultation questionnaires and the careful interrogations at interviews. Lactiplantibacillus plantarum PS128 (PS128) probiotic was administered to these physically healthy dogs with behavioral problems over a course of two weeks to determine the probiotic effectiveness on canine behaviors. Dogs were evaluated and scored using the Evaluation of Dog’s Emotional and cognitive Disorders (EDED) scale and the Canine Behavioral Checklist (CBC) questionnaire at the visits before and after the probiotic treatment. Plasma serotonin levels were measured using high-performance liquid chromatography- electrochemical detection (HPLC-ECD) and the serotonin turnover ratios (5-HIAA/5-HT) were compared pre- and post-treatment. The results showed that the general behavioral stability was improved, and the problems of aggression and separation anxiety were ameliorated after treatment. A significant decrease in 5-HIAA/5-HT ratio was observed in dogs with separation anxiety, suggesting a serotonin-related mechanism. These results proved that PS128 was beneficial for emotional stabilization, which might be useful as a therapeutic supplement for canine aggression and separation anxiety.
... De Napoli et al. [22] found that the addition of TRP to high protein diets or the switch to a low protein diet might reduce aggression in dogs displaying so-called dominance and territorial aggression. Plasma concentrations of 5-HT and TRP had consistent results in all phases of the study, despite different concentrations of dietary TRP. ...
Full-text available
These proceedings contain oral and poster presentations from various experts on animal behaviour and animal welfare in veterinary medicine presented at the conference.
... Moreover, TRP supplementation has been widely used as an effective therapy to alleviate behavior problems in animals. A low-protein diet supplemented with TRP is a solution to manage excessive aggression in dogs [133]. The detailed mechanism associated with this effect of TRP is still unclear but seems to be at least partly associated with the impact of its neuroactive metabolites. ...
Full-text available
Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress and mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that the activation of the kynurenine pathway (KP), caused by an activation of proinflammatory factors accompanying neurodegenerative processes, leads to the accumulation of its neuroactive and pro-oxidative metabolites. This leads to an increase in the oxidative stress level, which increases mitochondrial damage, and disrupts the cellular energy metabolism. This significantly reduces viability and impairs the proper functioning of central nervous system cells and may aggravate symptoms of many psychiatric and neurodegenerative disorders. This suggests that the modulation of KP activity could be effective in alleviating these symptoms. Numerous reports indicate that tryptophan supplementation, inhibition of KP enzymes, and administration or analogs of KP metabolites show promising results in the management of neurodegenerative disorders in animal models. This review gathers and systematizes the knowledge concerning the role of metabolites and enzymes of the KP in the development of oxidative damage within brain cells during neurodegenerative disorders and potential strategies that could reduce the severity of this process.
In this follow up study, we investigate a subset of 1,308 dogs whose owners (n = 1,048) described as having at least one form of fearful/anxious behavior. Using a self-reported questionnaire, owners were also asked to indicate the resolutions employed, including training methods and equipment, behavior modification programs, behavior modification and training techniques, medications, and forms of alternative medicine. Owners sought professional help for 50% of the fearful or anxious dogs. Nearly a quarter of the dogs were brought to a veterinarian for help; 15% of which were diagnosed with a medical condition contributing to the dog's misbehavior. Overall, reward-based training, mental stimulation, and habituation were associated with increased odds of improvement. For the specific fear/anxiety-based problems, various consultants and techniques or treatments were found beneficial. Inanimate fears benefited from the use of benzodiazepines, herbal remedies, and dietary changes. Animate fears had increased odds of improvement if the dog was brought to a behavior consultant, use of a relaxation protocol, and systematic desensitization. Situational fears benefitted from mental stimulation, a relaxation protocol, and short, frequent training sessions. Generalized anxiety had increased odds of improvement with nutraceutical therapy and enrollment in dog sporting activities. Negative odds of improvement were found if the dog had pre-existing aggression in conditions involving inanimate fears, situational anxiety, and post-traumatic stress disorder. Neutering (male or female) reduced odds of improvement for animate fears, as did consultation with a veterinarian or non-veterinary behaviorist and the use of benzodiazepines. Changes in management had a negative effect on treatment of situational fear/anxiety. Consulting a trainer and hormone therapy reduced odds of improvement with generalized anxiety disorder. Paradoxically, odds of improvement for post-traumatic stress disorder were reduced when increasing a dog's exercise level was employed in treatment.
The important biogenic amine, serotonin (5HT), was determined in whole blood, platelet-rich plasma (PRP), platelet-poor plasma (PPP), and plasma ultrafiltrate after simple deproteinization. Following ion-pair chromatography on standard or narrow-bore reverse-phase columns, 5HT and the internal standard(N-methylserotonin-NMS) were detected by flourometry with absolute detection limits of 2–4 pg. Levels obtained for whole blood and PRP were in agreement with previous methods. However, mean (±SD) values obtained for platelet-poor plasma (PPP) of 578±277 pg/ml (N=7) were approximately 3-fold lower than the lowest previous reports. We also report the first determination of 5HT in plasma ultrafiltrate, having observed mean levels of 387±222 pg/ml (N=7).
A new method for the concurrent assay of three tryptophan metabolites at the picomole level is described. The method has been developed for blood, urine, cerebrospinal fluid, and tissue samples such as whole brain, brain parts, and endocrine glands. Tryptophan itself, serotonin, and 5-hydroxyindoleacetic acid are isolated initially on extraction columns, eluted with a suitable solvent, and injected onto a liquid chromatograph with an amperometric detector. This general approach may be applicable to a variety of other tryptophan metabolites and should be useful in both research and clinical investigations.
The rates at which monoaminergic neurons in rat brains synthesize their neurotransmitters depend on the availability of the amino acid precursors tryptophan (for serotonin) and tyrosine (for dopamine and norepinephrine). The administration of tryptophan, the injection of insulin, or the consumption of a single protein-free high-carbohydrate meal all elevate brain tryptophan levels and, soon thereafter, the levels of serotonin and its major metabolite 5-hydroxyindole acetic acid. The addition of protein to the meal suppresses the increases in brain tryptophan and serotonin, because protein contributes to plasma considerably larger amounts of the other neutral amino acids (e.g., leucine, phenylalanine) than of tryptophan, and these other amino acids compete with tryptophan for uptake into the brain. The elevation of brain tyrosine (by injection of the amino acid or consumption of a single 40% protein meal) accelerates brain catecholamine synthesis, as estimated by measuring brain dopa accumulation after decarboxylase inhibition, or brain catecholamine accumulation after inhibition of monoamine oxidase. These observations suggest that serotonin- and catecholamine-containing brain neurons are normally under specific dietary control.
The influence of diet on human behaviour was first postulated several centuries ago, albeit in terms of a magical interpretation of life. Due to our improved knowledge of the basic science, we are now able to provide experimental proof to support this concept. Some opinions, which were once believed to be true, have now been disproved, whereas others have been reconfirmed in physiological terms. This paper aims to evaluate the state of the art in particular with regard to pediatrics. It is now certain that some amino-acids in the diet can influence brain activity by enhancing or reducing the metabolic rates of different neurotransmitters. A modulating effect on the brain has even been suggested with regard to some vitamins and minerals, but data on this aspect are still under evaluation. On the other hand, no data have yet been reported to support the hypothesis of a specific etiological role played by any nutrient in the development of behavioural disturbances.
1. Tryptophan increases 5HT synthesis, but the extent to which it increases 5HT release and therefore 5HT function is unclear. 2. The possibility that increased 5HT levels will lead to increased 5HT release is enhanced when 5HT neurons are firing at a higher rate. The rate of firing of 5HT neurons is increased as the level of behavioral arousal increases. Thus, altered tryptophan levels will be more likely to influence brain function at higher levels of arousal. 3. In the rat, tryptophan administration increased CSF 5HT appreciably when the animals were aroused by being put in the dark, but not when they were left in a lighted room. 4. In monkeys, the level of behavioral arousal does seem to influence the effect of altered tryptophan levels on aggression. This is consistent with the fact that altered tryptophan levels had no effect on aggression in normal subjects, but that tryptophan had a therapeutic effect in pathologically aggressive patients. 5. The confusing literature on the antidepressant effect of tryptophan can, to some extent, be explained by considering the circumstances in which tryptophan administration will lead to increases in 5HT release as well as increases in 5HT synthesis. 6. Although in some circumstances tryptophan can decrease pain perception by activation of spinal 5HT pathways, when it was given to postoperative patients it attenuated morphine analgesia by activation of a 5HT pathway in the brain. 7. The effect of altered tryptophan levels depend critically on the circumstances in which it is given.
The uptake of tyrosine into rat retina and brain was studied in vivo after its peripheral injection alone or in combination with other amino acids. Both retinal and brain tyrosine levels increased monotonically for at least 60 min after tyrosine administration. When tyrosine was injected along with branched-chain amino acids, but not with acidic amino acids, such increments in retinal and brain tyrosine levels were significantly attenuated. The postinjection tyrosine levels in retina and brain paralleled better the serum ratio of tyrosine to the sum of the other large neutral amino acids (which include the branched-chain amino acids) than the serum tyrosine level alone. These results suggest that tyrosine uptake into rat retina, like that into brain, is mediated by a competitive transport system shared among the large neutral amino acids.
Sympatho-adrenal (SA) activation was determined by measuring levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenal venous and peripheral venous plasma of 20 anesthetized cats following stimulation of medial hypothalamic sites. Hypothalamic sites were selected that elicited affective defense behavior in the freely moving cat. Fifty-eight percent of these hypothalamic sites elicited a bilateral increase greater than or equal to 10 ng/min in the output of both adrenal catecholamines (CAs); these increases were greater from the gland ipsilateral to the side of stimulation. Other SA responses included both preferential increases or decreases in either NE or E. Under baseline conditions, an average of 67% of the NE in the peripheral venous plasma was contributed by the sympathetic noradrenergic nerves; hypothalamic stimulation at "defense" sites increased the contribution to 75%. The data suggest that hypothalamic regions that elicit defense behaviour may overlap with regions that activate the adrenal medullary and sympathetic nervous systems.
We examined the effects of meals containing various proteins and carbohydrates, and of those containing various proportions of protein (0% to 20% of a meal, by weight) or of carbohydrate (0% to 75%), on plasma levels of certain large neutral amino acids (LNAA) in rats previously fasted for 19 hours. We also calculated the plasma tryptophan ratios (the ratio of the plasma tryptophan concentration to the summed concentrations of the other large neutral amino acids) and other plasma amino acid ratios. (The plasma tryptophan ratio has been shown to determine brain tryptophan levels and, thereby, to affect the synthesis and release of the neurotransmitter serotonin). A meal containing 70% to 75% of an insulin-secreting carbohydrate (dextrose or dextrin) increased plasma insulin levels and the tryptophan ratio; those containing 0% or 25% carbohydrate failed to do so. Addition of as little as 5% casein to a 70% carbohydrate meal fully blocked the increase in the plasma tryptophan ratio without affecting the secretion of insulin--probably by contributing much larger quantities of the other LNAA than of tryptophan to the blood. Dietary proteins differed in their ability to suppress the carbohydrate-induced rise in the plasma tryptophan ratio. Addition of 10% casein, peanut meal, or gelatin fully blocked this increase, but lactalbumin failed to do so, and egg white did so only partially. (Consumption of the 10% gelatin meal also produced a major reduction in the plasma tyrosine ratio, and may thereby have affected brain tyrosine levels and catecholamine synthesis).(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of dominance rank on the behavioral responses to drugs that enhance central serotonergic function were examined in 45 adult male vervet monkeys living in 15 stable social groups. Each group contained 3 adult males, 3 adult females, and their immature offspring. Dominance rank was assessed by measuring success in intermale agonistic encounters. In every group one male was clearly the dominant, or alpha male, and the other two males were subordinate. Males from 5 groups received 3 doses of the serotonin reuptake inhibitor fluoxetine (0.5, 1.0 and 2.0 mg/kg/day); those from a second set of 5 groups received 3 doses of the receptor agonist quipazine (0.25, 0.50 and 1.0 mg/kg/day); those from a third set of 5 groups received the serotonin precursor tryptophan (10, 20 and 40 mg/kg/day). The 3 drug treatments produced strikingly similar behavioral effects. Each produced dose-dependent increases in approaching, grooming, resting and eating and decreases in locomoting, avoiding, being vigilant and being solitary. Dominant males were significantly more responsive behaviorally to all 3 drugs than were subordinate males: the increase or decrease in each behavioral measure was larger in dominant than in subordinate males. In combination with previous studies, these data suggest that dominant and subordinate males differ in the drug sensitivity of their serotonergic systems.