Brain Research, 577 (1992) 194-199
© 1992 Elsevier Science Publishers B.V. All rights reserved. 0006-8993/92/$05.00
Repeated stressful experiences differently affect limbic dopamine
release during and following stress
Assunta Imperato a, Luciano Angelucci a, Paola Casolini a, Alessandro Zocchi b and
Stefano Puglisi-Allegra b
aInstitute of Medical Pharmacology, 2nd Chair, University 'La Sapienza', Rome (Italy) and blnstitute of Psychobiology and
Psychopharmacology [CNR], Rome (Italy)
(Accepted 19 November 1991)
Key words: Nucleus accumbens; Dopamine; Microdialysis; Chronic restraint stress; Adaptive mechanism
The effects of repeated restraint stress exposures (daily 60 min, for 6 days) on extraceltular dopamine in the nucleus accumbens, during
and after the stress experience, have been investigated in rats by in vivo microdialysis. On the first day, restraint increased dopamine release
during the first 40 rain followed by a return to basal levels (50-60 rain later). As soon as restraint ceased and the rats were set free, there
was another increase in dopamine release lasting 40 rnin. On the second and third day, restraint produced only a slight increase in dopamine
release, while no significant changes were evident from the fourth to the sixth day. By contrast, from the second to the sixth day the increase
in dopamine release observed once rats were freed, was unchanged in comparison to the first day. The present results show that the acti-
vation of the mesolimbic dopaminergic system induced by aversive stimuli adapts to repeated experiences differently from that produced by
pleasurable events, suggesting that aversive and rewarding experiences involve different neural systems.
A large body of evidence indicates that stressful ex-
periences alter dopamine (DA) metabolism and release
in the mesolimbic system l'SA°'ll'14-16,tS'23. Moreover, a
number of studies have shown that repeated exposure to
stress may lead to different responsiveness to subsequent
stressful experiences depending on the stressor as well
as on the stimuli paired with the stressor, either leading
to an unchanged or increased or decreased dopaminer-
gic mesolimbic function 4'9A2'21'22.
We have recently observed a rapid and transient in-
crease in DA release in the nucleus accumbens of re-
strained rats, the extracellular concentrations of DA re-
turning to basal levels after 50-60 min, although animals
were still restrained. Moreover, when animals were
freed, a considerable increase of DA release occurred
which is not related to motor activation 16. These find-
ings suggest that increased DA release in the mesolim-
bic system is a neurochemical correlate of emotional
arousal produced by sudden changes in environmental
stimuli, irrespective of their aversive (restraint) or posi-
tive (freeing) value. In particular, the end of restraint
may be considered a rewarding experience since pleasure
may also be experienced as a consequence of relief and
return to equilibrium 19. The above-mentioned results
seem consistent with the view that the activation of the
mesolimbic dopaminergic system produced by both aver-
sive and pleasant experiences is a general response re-
lated to increased arousability occurring in the presence
of sudden changes in the external environment.
Whether the mesolimbic dopaminergic system is the
brain system responsible for both aversive and pleasur-
able aspects of individual experience or, alternatively, is
the expression of different (and distinct) neural sub-
strates related to aversion and pleasure, is still a matter
of controversy 19. It seems to us that the study of the ad-
aptation of the two responses of the mesolimbic dopa-
minergic system to restraint and to relief from it, follow-
ing repeated stressful experiences, may shed some light
on this problem.
In the present study the effects of repeated restraint
on DA release in the nucleus accumbens during and af-
ter stress have been investigated by in vivo microdialysis
in order to assess if the dopaminergic mesolimbic system
adapts differently to repeated aversive (restraint) and
positive (freeing the animal) experiences.
MATERIALS AND METHODS
Male Sprague-Dawley rats (Charles River) were housed in
groups of 3 per cage for at least 10 days before use. Food and wa-
Correspondence: A. Imperato, Department of Neurosciences, Bernard B. Brodie, Via Porcell 4, 09124 Cagliari, Italy. Fax: (39) (70) 657237.
ter were freely available and animals were maintained under an ar-
tificial 07.00-19.00 h light-dark cycle. Experiments were carried out
between 09.00 and 14.00 h.
Microdialysis implantation and HPLC assay
Rats were anesthetized with chloralhydrate (0.4 g/kg i.p.) and
implanted with dialysis tubes (AN 69-HF, wet tube o.d. is 320/~m;
Hospal-Dasco, Bologna, Italy) at the level of the nucleus accum-
bens according to Krnig and Klippel atlas. Surgery was mainly
carried out as previously described 13'27 except that the dialysis tube
with a tungsten wire inside as a rigid support was directly held in
the micromanipulator of the stereotaxic instrument and inserted
into the nucleus accumbens, not connected to the stainless steel
cannula (o.d. 350 ~m). In order to do so, the dura mater was care-
fully removed to allow the insertion in the brain of the assembly
dialysis tube-tungsten wire. Once positioned in the nucleus accum-
bens, the tungsten wire was carefully pulled out so that no rigid
material was left in the brain. By avoiding the use of the steel can-
nula carrying the dialysis tube, the operation was less laborious,
with less steps in order to perform the insertion of the dialysis tube
in the brain. In fact, this procedure prevented the steel cannula-
fiber+tungsten assembly from being manipulated when cutting off
the steel cannula, once it left the brain. Therefore, less trauma and
tissue damage took place, so the glia reaction around the dialysis
tube was reduced allowing recovery of neurotransmitters from the
brain over several days after its insertion.
A similar surgical procedure has already been described by Dams-
Ringer solution (in mM: KC1 4, NaCI 147, CaCI 2 1.5) was
pumped through the dialysis tubes at a constant rate of 2 #l/rain.
Dopamine with its main metabolites, dihydroxyphenylacetic acid
(DOPAC) and homovanillic acid (HVA) were estimated in 10 min
samples (20/A) of dialysate by high-performance liquid chromatog-
raphy (HPLC) with electrochemical detection according to the
technique described previously 13. The analytical column was a Su-
pelco LC-18-DB column 3.3 cm long, 4.6 mm large and with a
packing material 3/~m in size. The detection limit for DA was 0.002
Experiments started 24 h after the implantation of the dialysis
Restraint stress procedure
After 2 h of perfusion, when the output of the neurotransmitters
had become stable (the last 3 samples not differing by more than
10%), the rat was restrained by placing it in a plexiglas box (9 × 7
x 15 cm) for 60 min 14-16. The restraint apparatus was provided
with a sliding surface allowing animals to be gently handled during
both restraining and releasing procedure 23. Samples were collected
every 10 min throughout restraint (60 min) as well as when the an-
imals were set free (60 min). This procedure was carried out for 6
consecutive days, and after 3 resting days, it was applied again on
the 10th day from the onset of the restraint schedule.
Effect of haloperidol in chronically implanted rats
In order to assess the efficiency both of the novel cannula im-
plantation and of the functional state of the dopaminergic system
throughout 10 days after the surgery, an additional group of rats
were implanted according to the revised procedure, and, on them,
the effect of haloperidol on the extracellular concentrations of DA
and metabolites on day 1 (24 h after the implantation), day 5 and
day 10, was tested.
In order to assess the amount of glia reaction around the dialysis
tube inserted into the nucleus accumbens according to the revisited
technique, in comparison with the previous one, rats implanted
with both techniques 10 days before, were perfused with intracar-
diac formalin (10% solution in saline) under chloralhydrate anes-
thesia. Sagittal sections of the brains were incubated with glial
fibrillary acidic protein (GFAP) and myelin basic protein (MBP) to
stain the amount of gliosis reaction and tissue damage. Other sec-
tions were stained with Luxol-fast Cresyl violet to verify microan-
The extent of the gliosis reaction was evaluated by counting the
number of GFAP-positive glial cells in rats implanted with the re-
visited technique or with the former one. Briefly, 5 serial sections
per animal (n = 4 per each technique) were examined under a light
microscope at a final magnification of x250. The area of the nu-
cleus accumbens was delineated using an image analyzer (Video-
plan, Kontron-Zeiss, FRG) connected via a "IV camera with the
microscope. The number of GFAP-positive cells was counted in the
entire area of the nucleus accumbens by two experienced observ-
ers unaware of the two different techniques considered.
Data were analyzed by repeated measure ANOVA. Individual
between-group comparisons (where appropriate) were carried out
using Student's t-test (two tailed) for paired data.
As shown in Fig. 1, on the first day a considerable in-
crease in the extracellular concentration of DA and me-
tabolites occurred during the first 40 min of restraint (the
maximal increase was at 20 min), followed by a return
to basal levels (50-60 min). As soon as restraint ceased
and the rats were set free, there was a sudden increase
of DA release as well as of DOPAC and HVA, lasting
40 min. It is worth noting that freed animals did not
show higher behavioral activity (locomotion, stereotyp-
ies) than that exhibited in the period preceding restraint.
On the second and third day, restraint produced only
a slight increase in the release of DA and metabolites.
No significant changes in DA and metabolites were ev-
ident from the fourth to the sixth day.
By contrast, from the second to the sixth day the in-
crease in DA, DOPAC and HVA observed once rats
were freed, was unchanged in comparison with the first
Following 3 days of rest after the last stressful experi-
ence, when animals were retested (10th day), restraint
produced an increase in DA, DOPAC and HVA similar
to that observed on the first day. Moreover, the increase
in DA release following the end of restraint paralleled
that observed on previous days.
Fig. 2 shows the time-course of the extracellular con-
centrations of DA, DOPAC and HVA in the nucleus
accumbens over 10 days. Data refer to baseline values
of unstressed rats (n = 7), which were not significantly
different from the group of rats tested for restraint dur-
ing ten days after surgery. On the first 3 days following
the operation there was a decrease in DA, DOPAC and
HVA, while from the fourth day onward they reach sta-
ble values at least up to the tenth day. Elimination of
Ca 2+ from the Ringer solution perfusing the accumbens
induced a dramatic decrease of DA release on the first
day (as shown also for the striatum, ref. 13) as well as
1 =t day
0 _T~-restralnt --~
I I ' I ' ' 1 ' ' t
3 rd day
0 ._~r-~--restraint -~
I " ' I ' '
' ' I
5 th day
' I ~ ' I ' ~ I ' ~ I
0 30 60 90 120
10 th day
0 ~ I- restraint "-1
I ' ' ' 1 ' I ' '
0 30 60 90 120
2 "d day
0 _-I-~--restralnt ---,
I ' I ' , f
4 th day
150 ** .
I , ' I ' ' I
6 th day
150 ** .
0 --1-1~restraint --I
I ~ I I
0 30 60 90 120
Fig. 1. Changes in dopamine (DA) (O), dihydroxyphenylacetic acid (DOPAC) (A) and homovanillic acid (HVA) (4) output in the nucleus
accumbens induced by 60 min restraint stress and subsequent liberation of animals (n = 9), each day for 6 days, and again, after 3 days of
rest. Results are expressed as mean (+ S.E.M.) percent of basal values. +P < 0.05, *P < 0.01, **P < 0.001 vs. basal values. For details see
on the following days (not shown).
The morphology of sections of the rat nucleus accum-
bens is better preserved in animals implanted with the
revisited technique. Table I summarizes the values of the
density of GFAP-positive glial cells in the nucleus ac-
cumbens of rats implanted with the revisited technique
or with the former one. The number of glial cells dis-
playing GFAP immunoreactivity in rats implanted with
the former technique was about 60% higher than that
observed in animals implanted with the revisited one.
In order to test the performance of the mesolimbic
dopaminergic system in these long-term implanted rats,
we assessed the effects of haloperidol 24 h, 5 days and
10 days after surgery. Fig. 3 shows the effects of a chal-
lenge dose of haloperidol (0.1 mg/kg s.c.) on DA release
and metabolism. As shown, the effects are very similar
for the 3 days suggesting that on the days following the
operation there is no alteration in the ability of the lim-
bic dopaminergic system to respond to receptor block-
nucleus eccumbens a
0 i 2 3 4 5 6 10 0
DAYS AFTER OPERATION
Fig. 2. Time-course of DA (O), DOPAC () and HVA (A) out-
put in the nucleus accumbens starting from 24 h up to 10 days af-
ter the dialysis tube implantation. Results are expressed as pmol/10
rain samples (20/d) of dialysate (mean _+ S.E.M. of 7 rats). Filled
symbols, P < 0.05 in comparison with the previous day.
The present results show that both restraint and the
cessation of the stressful experience produce an increase
of DA release in the nucleus accumbens, thus confirming
our previous report 16. However, repeated (daily) stress-
ful experiences produced a gradual reduction in the ef-
fects of stress on DA release which were abolished from
the fourth day onward. By contrast, the enhancement of
DA release produced by setting the animals free, was
unchanged from day 1-6. Consequently, it could be hy-
pothesized that the enhancement of DA release in the
nucleus accumbens may be regulated by different fac-
Density of GFAP-positive glial cells in the nucleus accumbens of
rats with different implantation methods
The values are means + S.E.M. In brackets, the number of ani-
mals. For details see text (Materials and Methods).
GFAP-positive cells~200 ltm 2
480 _+ 25 a
290 _+ 15
ap < 0.001 vs. revisited technique.
tors, depending on the nature of the environmental stim-
After 3 days of resting from the last stressful experi-
ence, when animals were retested (10th day), the effects
of restraint stress on DA release were similar to those
observed on the first day indicating a recovery of respon-
siveness to stress following a resting period. No sensiti-
zation to the effects of stress was observed in agreement
with a previous report in which different experimental
design and neurochemical analysis were used 17. The ef-
fects observed on the tenth day also indicate that the
absence of response to stress observed in previous days
was not to be ascribed to malfunctioning of the chroni-
cally implanted dialysis tubes, or to a decreased effi-
ciency of the dopaminergic system.
Therefore, this study shows that transversal microdi-
alysis allows subchronic studies to be performed for at
least 10 days after surgery. As shown, the extracellular
concentrations of both DA and metabolites tend to de-
0 DA D DOPAC n HVA
1" day 5 th day 10 th day
400 ****** **,,* * **
0 60 120 180 240 300 0 60 120 180 240 300 0 60 IzO 189 24:) ?~)
Fig. 3. Effects of haloperidol (0.I mg/kg s.c.) on DA (O), DOPAC (IS]) and HVA (A) from the nucleus accumbens 24 h, 5 days and 10 days
after surgery. Arrows indicate time of drug administration. Results are expressed as mean (_+ S.E.M.) percent of basal values, n = 5 for
each day. +P < 0.01, *P < 0.001 vs. basal values. For details see text.
crease during the first 3 days after surgery, but after-
wards DA, DOPAC and HVA reach stable values which
are maintained in the following 10 days, and for up to
more than 3 weeks (Imperato et al., in preparation).
Moreover, the histological appearance of the tissue
around the dialysis tube shows much less gliosis reaction
in comparison to that observed with the previous surgi-
cal technique. This may allow a better diffusion of neu-
rotransmitters from the tissue to the dialysis tube mak-
ing possible, indeed, their detection for a longer time
after the implantation.
Moreover, with the knowledge that drugs which block
DA receptors induce a full activation of the dopaminer-
gic system expressed as an increase of DA synthesis,
metabolism and release 2'3'6'13'24'26, we used a haloperi-
dol-challenge to test the performance of the dopaminer-
gic system on the 1st, 5th and 10th day after the oper-
ation. The results show that the increase in DA release
and metabolism was similar over the days studied, sug-
gesting that no alterations in the activity of the dopami-
nergic system have taken place.
The present results indicate that activation of the me-
solimbic dopaminergic system produced by aversive stim-
uli adapts to repeated experiences differently from that
produced by pleasurable events, possibly due to the fact
that aversive experiences involve neural elements that
undergo habituation more rapidly than those involved in
pleasurable experiences. It may also be that neural and
behavioral activation z° related to rewarding stimuli, are
resistant to habituation because of the value that most
rewarding stimuli have for the organism. Accordingly,
mesolimbic dopaminergic activation may be related to
reinforcing properties of rewarding experiences 19, which
would maintain it at a high level throughout repeated
Further studies focused on other rewarding experi-
ences (e.g. feeding, sexual behavior) could elucidate this
The increase in DA release produced by restraint may
be the expression of an arousal response elicited by en-
vironmental changes perceived by the organism 7'25. Since
arousal undergoes rapid habituation, the diminished in-
crease in DA release following restraint, observed from
the second daily experience onward, strongly suggests
that this is the case. Furthermore, habituation rapidly
disappears in the absence of the stimulus producing it2°;
consistent with this hypothesis our present results show
that, after 3 days of resting, when the animals were again
subjected to restraint, the response of the limbic dopa-
minergic system was similar to that observed after the
first stressful experience.
Moreover, the increased DA release in the nucleus
accumbens may be related to the meaning that aversive
conditions have for the organism. As the animal faces
environmental changes leading to a discrepancy between
expected and observed events, it will first attempt to
cope behaviorally with such a pressure, in order to re-
instate the previous equilibrium. Therefore, the arousal
response is accompanied by activation directed toward
responding to environmental pressure 2°, which may have
a neurochemical correlate in the enhancement of DA
release in limbic areas. But, when, as in case of our ex-
perimental conditions, the efforts of the organism do not
lead to controlability of the environment throughout
daily stressful experiences, an habituation occurs and
therefore a gradual decrease of the dopaminergic re-
Our findings that increase in DA release in the nucleus
accumbens adapts differently to aversive or pleasurable
repeated experiences suggest that such an increase is re-
lated to an involvement of different neural systems. This
hypothesis is in agreement with the view of other au-
thors 19 who have recently proposed that more than one
set of neurons and more than one neuronal system are
necessary to integrate reward, pleasure or reinforcement,
as well as aversion.
Therefore, our findings in vivo suggest that although
the activation of the dopaminergic system in limbic ar-
eas may be considered a neurochemical correlate of
emotional activation related to positive or negative ex-
periences, it is not a general response to perceived
changes in environmental stimuli but rather a response
related to the activation of selective neuronal systems
involved in the evaluation of the meaning that external
stimuli have for the organism. Consequently, the nucleus
accumbens, one of the most important stations in the
neural mechanisms that govern behavior and emotions,
may be influenced by different neuronal systems depend-
ing on the stimuli which the organisms receives and, in
turn, may transmit them to other effectors providing the
physiological expression of behavior and emotions.
Lastly, the study of these neuronal systems may shed
some light also on the understanding of pathological
emotional states such as helplessness and anhedonia.
Acknowledgements. We wish to thank Dr. Elia Perentes, Sandoz
Ltd, Basle, Switzerland, who helped us with the immunohistochem-
ical staining of the brains, and Dr. Francesco Amenta, Diparti-
mento di Scienze Neurologiche, Universit~t 'La Sapienza', Roma,
Italia, who helped us in the quantification of gliosis reaction.
REFERENCES Download full-text
I Abercrombie, E.D., Keefe, K.A., DiFrischia, D.F. and Zig-
mond, M.J., Differential effects of stress on in vivo dopamine
release in striatum, nucleus accumbens, and medial prefrontal
cortex, J. Neurochem., 52 (1989) 1655-1658.
2 Anden, N.E., Dopamine turnover in the corpus striatum and
limbic system after treatment with neuroleptics and acetylcho-
line drugs, Eur. J. Pharmacol., 24 (1972) 905-906.
3 Bunney, B.S., Waiters, J.R., Roth, R.H. and Aghajanian,
G.K., D-Amphetamine induced inhibition of central dopaminer-
gic neurons: mediation by a striatonigral feedback pathway, J.
Pharmacol. Exp. Ther., 195 (1973) 560-571.
4 Cabib, S., Kempf, E., Schleef, C., Mele, A. and Puglisi-Alle-
gra, S., Different effects of acute and chronic stress on two do-
pamine-mediated behaviors in the mouse, Physiol. Behav., 43
5 Cabib, S., Kempf, E., Schleef, C., Oliverio, A. and Puglisi-Al-
legra, S., Effects of immobilization stress on dopamine and its
metabolites in different brain areas of the mouse: role of gen-
otype and stress duration, Brain Res., 441 (1988) 153-160.
6 Carlsson, A. and Lindqvist, M., Effects of chlorpromazine or
haloperidol on formation of 3-methoxytyramine and normetha-
nephrine in mouse brain, Acta Physiol. Scand., 20 (1963) 140-
7 Cole, B.J. and Robbinson, T.W., Effects of 6-hydroxydopamine
lesions of the nucleus accumbens septi on performance of a
5-choice serial reaction time task in rat: implication for theories
of selective attention and arousal, Behav. Brain Res., 33 (1989)
8 Damsma, G. and Westerink, B.H.C., A microdialysis and au-
tomated on-line approach to study central cholinergic transmis-
sion in vivo. In T.E. Robinson and J. Justice (Eds.), Microdi-
alysis in the Neurosciences, Elsevier, Amsterdam, 1991, pp.
9 Deutch, A.Y., Tam, S. and Roth, R., Footshock and condi-
tioned stress increase 3,4 dihydroxyphenylacetic acid (DOPAC)
in the ventral tegmental area but not in the substantia nigra,
Brain Res., 33 (1985) 143-146.
10 Dunn, A.J. and File, S.E., Cold restraint stress alters dopamine
metabolism in frontal cortex, nucleus accumbens and neostria-
turn, Physiol. Behav., 31 (1983) 511-513.
11 Fadda, E, Argiolas, A., Melis, M.R., Tissari, A.H., Onali, P.L.
and Gessa, G.L., Stress-induced increase in 3,4-dihydroxyphe-
nylacetic acid (DOPAC) levels in the cerebral cortex and in the
nucleus accumbens: reversal by diazepam, Life Sci., 23 (1978)
12 Herman, J.P., Guillonneau, D., Dantzer, R., Scatton, B., Se-
merdjian-Rouquier, L. and Le Moal, M., Differential effects of
inescapable footshocks and of stimuli previously paired with in-
escapable footshocks on dopamine turnover in cortical and lim-
bic areas of the rat, Life Sci., 30 (1982) 2207-2214.
13 Imperato, A. and Di Chiara, G., Dopamine release and me-
tabolism in awake rats after systemic neuroleptics as studied by
trans-striatal dialysis, J. Neurosci., 5 (2) (1985) 297-306.
14 Imperato, A., Puglisi Allegra, S., Casolini, P., Zocchi, A. and
Angelucci, L., Stress-induced enhancement of dopamine and
acetylcholine release in limbic structures: role of corticosterone,
Eur. J. Pharmacol., 165 (1989) 337-338.
15 Imperato, A., Puglisi-Allegra, S., Zocchi, A., Scrocco, M.G.,
Casolini, P. and Angelucci, L., Stress activation of limbic and
cortical dopamine release is prevented by ICS 205-930 but not
by diazepam, Eur. J. Pharmacol., 175 (1990) 211-214.
16 Imperato, A., Puglisi-Allegra, S., Casolini, P. and Angelucci,
L., Changes in brain dopamine and acetylcholine release dur-
ing and following stress are independent of the pituitary-adreno-
cortical axis, Brain Res., 538 (1991) 111-117.
17 Kalivas, P.W. and Duffy, P., Similar effects of daily cocaine and
stress on mesocorticolimbic dopamine neurotransmission in the
rat, Biol. Psychiatry, 25 (1989) 913-928.
18 Kramarcy, N.R., Delanoy, R.L. and Dunn, A.J., Footshock
treatment activates catecholamine synthesis in slices of mouse
brain regions, Brain Res., 290 (1984) 311-319.
19 Le Moal, M. and Simon, H., Mesocorticolimbic dopaminergic
network: functional and regulatory roles, PhysioL Rev., 71(1)
20 Pribram, K.H. and McGuinness, D., Arousal, activation, and
effort in the control of attention, Psychol. Rev., 82(2) (1975)
21 Puglisi-Allegra, S. and Cabib, S., Effects of defeat experiences
on dopamine metabolism in different brain areas of the mouse,
Aggr. Behav., 14(4) (1990) 523-528.
22 Puglisi-Allegra, S., Kempf, E. and Cabib, S., Role of genotype
in the adaptation of the brain dopamine system to stress, Neu-
rosci. Biobehav. Rev., 14(4) (1990) 523-528.
23 Puglisi-Allegra, S., Imperato A., Angelucci, A. and Cabib S.,
Acute stress induce time-dependent responses in the dopamine
mesolimbic system, Brain Res., 554 (1991) 217-222.
24 Scatton, B., Garret, C. and Julou, L., Acute and subacute ef-
fects of neuroleptics on dopamine synthesis and release in the
rat striatum, Naunyn-Schmiedeberg's Arch. Pharmacol., 289
25 Simon, H. and Le Moal, M., Mesencephalic dopaminergic neu-
rons: functional role. In E. Usdin, A. Carlsson and J. Engel
(Eds.), Catecholamines: Neuropharmacology and Central Ner-
vous System-Theoretical Aspects, Part B, Adrian Liss, New
York, 1984, pp. 297-307.
26 Zetterstr0m, T., Sharp, T. and Ungerstedt, U., Effects of neu-
roleptic drugs on striatal dopamine release and metabolism in
awake rats studied by intracerebral dialysis, Eur. J. Pharmacol.,
106 (1984) 27-37.
27 Zetterstr0m, T. and Ungerstedt, U., Effects of apomorphine on
the in vivo release of dopamine and its metabolites, studied by
brain dialysis, Eur. J. Pharmacol., 97 (1984) 29-36.