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Response to Acute Stress in Domestic Cats Using Synthetic Analogues of Natural Appeasing Pheromones with Nepeta cataria Extract Rich in Nepetalactone: A Double-blinded, Randomized, Positive Controlled Cross-over Study

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Background Olfactory communication in cats is of major importance. It is rather complex and includes pheromone-driven and classical odour-based communication. Cats use various marking behaviours to transmit pheromone signals: appeasing markings that have a calming effect and alarm markings that can exacerbate stress. On the other hand, classical odours could possibly complete, modify, synergise, or add to pheromone-driven communication in felines, including in the domestic cat. One of the best known natural odours able to produce an identified behavioural sequence in Felidae is nepetalactone, from Nepeta plant species. A relationship is suspected to exist between nepetalactone and pheromone production in cats. We hypothesised that nepetalactone may have a synergistic or additive action with appeasing pheromones in domestic cats.
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Intern J Appl Res Vet Med • Vol. 13, No. 2, 2015. 125
KEY WORDS: behaviour, cat, pheromone,
nepetalactone, odour, F3 fraction, Zenifel
ABSTRACT
Background
Olfactory communication in cats is of
major importance. It is rather complex and
includes pheromone-driven and classical
odour-based communication. Cats use vari-
ous marking behaviours to transmit phero-
mone signals: appeasing markings that have
a calming effect and alarm markings that can
exacerbate stress. On the other hand, classi-
cal odours could possibly complete, modify,
synergise, or add to pheromone-driven
communication in felines, including in the
Response to Acute Stress in Domestic Cats
Using Synthetic Analogues of Natural
Appeasing Pheromones with Nepeta cataria
Extract Rich in Nepetalactone:
A Double-blinded, Randomized, Positive
Controlled Cross-over Study
Natalia Bernachon1
Claude Beata2
Nolwenn Crastes3
Patricia Monginoux4
Hugues Gatto4
David McGahie1
1Medical Department Virbac, Carros, France
2Dip. ECVBM-CA, CETACE SARL
341 boulevard Grignan
Toulon 83000, France
3R&D Virbac, Carros, France
4UPL Virbac, Carros, France
Virbac, 13ème Rue, Carros 06511, France
Corresponding author:
natalia.bernachon@virbac.com
Vol. 13, No.2, 2015 • Intern J Appl Res Vet Med.
126
domestic cat. One of the best known natural
odours able to produce an identied behav-
ioural sequence in Felidae is nepetalactone,
from Nepeta plant species. A relationship
is suspected to exist between nepetalactone
and pheromone production in cats. We
hypothesised that nepetalactone may have a
synergistic or additive action with appeasing
pheromones in domestic cats.
Methods
The present study compared the impact
of synthetic analogues of feline appeasing
pheromones combined with a Nepeta cataria
extract rich in nepetalactone (ZENIFEL®
spray) to a positive control consisting of
synthetic analogues of feline appeasing
pheromones alone (FELIWAY® spray) on
acute stress in domestic cats.
Results
Differences were observed between the
positive control and Zenifel® at various
time points. Zenifel® provided a statisti-
cally signicant reduction in the stress index
compared to the positive control (p=0.029)
during the central stressful event (blood
pressure measurement).
Conclusion
The association of synthetic analogues of the
F3 fraction of feline facial pheromones and
nepetalactone allows better management of
moderate acute stress in domestic cats than
analogues of feline facial pheromones alone.
This may be a useful new tool for the tar-
geted management of moderate behavioural
disorders.
BACKGROUND
Communication in domestic carnivores
involves multiple modalities, and olfactory
communication is among one of the most
important.1,2 This form of communication
is rather complex and takes place at various
levels. An important difference has been
determined in the past 20 years between
simple smells and pheromone-driven com-
munication.1 Pheromones are chemical
substances,1,3 and they are secreted in very
small quantities by some species. They have
particular olfactory characteristics and do
not act as only an olfactory stimulus.1 In
the earliest publications pheromones were
classed as natural social odours.4 Phero-
mones are also described as olfactory cues
and trigger highly species-specic non-
learned (innate) social responses.3 They are
detected in several mammals, including cats,
by a specic organ, the vomeronasal organ
(VNO), which is dened as an accessory
olfactory tract. The odour of the pheromones
can be a chemical stimulus that induces the
opening of the VNO.1, 5
The order of carnivora has the greatest
variety of glands secreting these chemical
signals.1 Sources of pheromones in Felidae
include the perianal complex, facial glands,
interdigital glands, genital complex, urine,
and faeces.1,4 In the cat, ve different facial
pheromone fractions named Fl to F5 have
been isolated1,6 from the sebaceous secre-
tions of the cheeks. The function in territo-
rial marking behaviour of the F2, F3, and
F4 fractions of facial pheromones is well
described in cats.1 Synthetic analogues of F3
and F4 are successfully used to manage mild
behavioural disorders such as inappropriate
urinary marking3,7,8 and scratching of furni-
ture,3 facilitate cohabitation,1 socialisation,1
avoid fear,3,9 and possibly reduce the overall
sense of anxiety in cats.9
On the other hand, olfactory communi-
cation in cats cannot be reduced to only the
pheromone side. The inuence of classical
odours is also important in feline behav-
iour.2,10 Over recent years, with attention
being focused on pheromone-driven com-
munication, this type of olfactory stimulus
has been to some extent “forgotten” by vet-
erinary science. Nevertheless, some odours
are known to induce a specic repeatable be-
havioural response with unique behavioural
patterns. Multiple chemical substances from
diverse biological sources can elicit unique
patterns of behaviour in most species of the
family Felidae.
One publication4 cited 14 chemical com-
pounds having a behavioural impact or/and
crossed reaction with natural social odours
(pheromones). From the chemical point
Intern J Appl Res Vet Med • Vol. 13, No. 2, 2015. 127
of view they form three different groups
(methylcyclopentanoid monoterpenes,
monoterpenoid alkaloids, and 4-methyl-
benzofuranones), all able induce what we
call the “catnip response” consisting of four
components:
1. snifng
2. licking and chewing with head
shaking
3. chin and cheek rubbing, and
4. rolling over and body rubbing.11
Although none of these behaviours are spe-
cic or unique to this response, the sequence
remains almost invariable in domestic and
wild felines.4,12,13 The name “catnip re-
sponse” comes from the best-known natural
odour able to induce this response,4,14 the cy-
clic lactone nepetalactone, found in Nepeta
plant species (for exemple Nepeta cataria),
or its isomeres that are found in Actinidia
species (dihydronepetalactone, isodihy-
dronepetalactone, and neonepetalactone).4
Nepetalactone has also been reported to be
found in some other plant species.4,14
One of the most interesting questions is
the physiological nature of the nepetalactone
response in felines. Some results indicate a
peripheral nicotinic and central muscarinic
cholinoceptive and serotonergic facilitation
of the catnip response.15 Oral administra-
tion of encapsulated nepetalactone (20 to
80mg) does not induce the response,16 nor
does taste or parenteral administration.4
The nepetalactone response is restricted to
simple olfactory stimulation in cats, without
involvement of the vomeronasal organ.13
Separately, the behavioural components
of this response are also seen in feeding or
sexual behaviour. However the response in
itself is independent of the presence of the
gonads17 and clearly associated with plea-
sure in the cat.15,18,19 The response has not
been found in other animals, and is consid-
ered to be specic to Felidae.4 The question
arises whether this natural compound could
cross-react with pheromone communication
in Felidae, and if so, in what way.
The hypothesis has been advanced that
the nepetalactone reaction is a response to an
additional stimuli in pheromone-driven com-
munication.4,12 It is still unknown whether
it stimulates natural pheromone production,
modies perception, or even simply rein-
forces the message delivered by the specic
olfactory pheromone-driven stimulation.
The nepetalactone odour is highly attractive
for various felines (domestic and wild)19 in
a dose dependant manner and even at weak
dosages for the domestic cat (0.1-0.01 mg),
while interest decreases toward the dosage
of 0.001 mg.19 Exposure to nepetalactone
containing substances increases overall well-
being in cats, facilitates play-like behaviour
and social interaction,2 and induces calming
effects.20
Based on the currently available litera-
ture, we hypothesised that nepetalactone
may have a synergistic or additive action
with appeasing pheromones, by reinforc-
ing the message delivered by pheromones
or stimulating the production of natural
appeasing pheromones. In order to verify
if there could be an additive or synergistic
effect, we conducted a study with domestic
cats. The positive control cats received the
currently commercially available synthetic
analogues of feline appeasing pheromones
(FELIWAY® spray) and other cats received
a new combination of synthetic analogues
of feline appeasing pheromones combined
with a Nepeta cataria extract as a source of
nepetalactone (ZENIFEL® spray).
METHODS
General Design
This was a double-blinded, crossover, ran-
domised, single centre, positive controlled
efcacy study. The study was carried out in
accordance with the relevant legislation on
animal experimentation and Virbac’s chart
of Ethics.
Animals
The study was done with 24 healthy adult
cats (at least 12 months old), divided into
four small groups, all living in an enriched
(special feline toys and scratching support
material) experimental environment. The
Vol. 13, No.2, 2015 • Intern J Appl Res Vet Med.
128
groups of cats were formed 2 weeks prior to
the start of the study. Each group included
three females and three males, with only one
intact male in each group. The 24 cats in-
cluded in the study were ranked within sexes
in descending order of their human manipu-
lation acceptance score (the lowest possible
score was 1, and the greatest 10).
Cats included in the study were consid-
ered to be stable from a behavioural point of
view with an individual human manipulation
score of between 6 and 9, and no difference
between groups in their mean score.
Before the study all animals were treated
against the most common internal and exter-
nal parasites, and were tested for common
infectious diseases including FIV and FeLV.
All cats were naive regarding blood pressure
measurement.
Products
The positive control was Feliway® spray 20
ml (Ceva, France), which contains synthetic
analogues of Fraction F3 of the feline facial
pheromone (10%).
The test product was Zenifel® spray
20 ml (Virbac, France), which contains
synthetic analogues of Fraction F3 of the
feline facial pheromone (10%) and extract of
Nepeta cataria 0.5%.
The two products were administered
using identical spray (20ml) applicators
labelled in a blinded manner. An identical
proportion and amount of F3 fraction con-
tained in the two mixtures used.
Study Schedule
The study included test and administration
periods of 5 days (described in Table 1),
and a washout period of at least 9 days. Two
groups received the test product rst, and
two groups received the positive control
rst. All cats then changed to the other
product such that each product was tested
by all 24 cats. The central stressful event
was human manipulation and blood pres-
sure measurement (oscillometric Cardell BP
Monitor), which had never been performed
before on these cats.
The study was conducted in four identi-
cal separate study rooms, each with a high
ow ventilation system in which there was
no sharing of air between rooms. The cats
rotated between the rooms to remove any
risk of cross contamination, and thus, an
extended carry-over effect. At the beginning
of each wash-out period, each room and the
material in the room were cleaned in order
to eliminate as much as possible the residues
of the product. The scratching materials
were changed.
Blood pressures were taken before the
rst administration of the product at the day
1 of the administration period, and at the day
5 of the administration period. The products
were sprayed in ve applications (product
volume 0.15 ml per application) in each
corner of the study room on three occasions
per administration day (at approximately 8
AM, 12 noon and 4 PM). The products were
Test and administration period
Day Blood pressure
measurement and
human
manipulation
Product
administration
Behavioural
assessment
D1 Yes (initial) No Yes (4 time points)
D2 No Yes (3 times) No
D3 No Yes (3 times) No
D4 No Yes (3 times) No
D5 Yes (nal) Yes (3 times) Yes (4 time points)
Table 1: Schedule of events during the test and administration periods
Intern J Appl Res Vet Med • Vol. 13, No. 2, 2015. 129
applied to the wall from the bottom corner
up to a height of 2 meters.
Behavioural and Stress Assessments
The staff that performed these assessments
had received specic behavioural training
prior to the onset of the study. Acceptance
of blood pressure measurement and overall
human interaction/handling was assessed
during blood pressure measurement using an
appropriate score chart (Table 2).
Another chart was used to access behav-
ioural observations 30 – 40 minutes before
manipulation, and then 30 – 40 minutes and
4 – 5 hours after manipulation (Table 3).
Both score charts (Tables 2 and 3) for
the behavioural evaluation were prepared
by a specialist in behaviour. The mean score
per cat obtained from the observations in the
charts above provided the wellbeing score
of each individual cat. The stress index was
obtained by subtracting the actual well being
score from the maximum possible score.4
Acceptance of blood pressure measurement
Behavioural & somatic signs
Behavioural sequence/attitude Never Once or for a
short period
Few (1< >5)
or for a long
time
Many (>5)
or mostly/all
of the time
1. Dilated pupils 4 3 2 1
2. Startled, aroused, hyper
vigilant
4 3 2 1
3. Salivation 4 3 2 1
4. Feet sweating 4 3 2 1
5. Trembling 4 3 2 1
6. Polypnea, panting 4 3 2 1
7. Tail icking-thumping 4 3 2 1
8. Frenetic self-licking 4 3 2 1
9. Emotional elimination (mictu-
rition or diarrhoea)
4 3 2 1
10. Attempting to ee 4 3 2 1
11. Facial marking on objects 1 2 3 4
12. Appeased self-grooming 1 2 3 4
13. Spontaneous contact with
manipulator (allomarking, play or
just contact)
1 2 3 4
14. Sitting on all four legs, tense
body posture and backward-
rotated ears
4 3 2 1
15. Threatening vocalizations
(hissing, spitting, growling) or
rolling over with attened ears
(ready to launch a paw strike)
4 3 2 1
16. Paw strike/ Attempting to
bite
4 3 2 1
Table 2: Behavioural assessment record: observation sheet during blood pressure measure-
ment with immediate responses
Vol. 13, No.2, 2015 • Intern J Appl Res Vet Med.
130
In order to assess the impact of the new
formulation (Zenifel®), we calculated the
mean stress scores per product (Zenifel®
and the Feliway® positive control) at dif-
ferent time points (30 – 40 minutes before
manipulation, during manipulation, and then
30 – 40 minutes and 4 – 5 hours after ma-
nipulation) on day 1 and again on day 5. We
then calculated the arithmetical change (day
5 - day 1) and the relative change ((day 5-
day 1)/day 1) in stress scores for each group,
at each time point, and compared the mean
Behavioural & somatic signs
Behavioural sequence/attitude
Never Once or
for a short
period
Few (1< >5)
Or for
a long time
Many (>5)
or mostly/all of
the time
1. Dilated pupils 4 3 2 1
2. Startled, aroused, hyper
vigilant
4 3 2 1
3. Salivation 4 3 2 1
4. Feet sweating 4 3 2 1
5. Trembling 4 3 2 1
6. Polypnea, panting 4 3 2 1
7. Rolling Skin Syndrome 4 3 2 1
8. Tail icking-thumping 4 3 2 1
9. Frenetic self-licking 4 3 2 1
10. Cat staring at the observer 4 3 2 1
11. Emotional elimination 4 3 2 1
12. Spraying, Scratching 1 2 3 4
13. Facial marking on objects 1 2 3 4
14. Eating 1 2 3 4
15. Relaxed rest 1 2 3 4
16. Appeased self-grooming 1 2 3 4
17. Spontaneous contact with
observer
1 2 3 4
18. Induced contact with
observer after the
4 3 2 1
19. Sitting on all four legs,
tense body posture
4 3 2 1
20. Threatening vocalizations 4 3 2 1
21. Rolling over with at-
tened ears
4 3 2 1
22. Paw strike/ Attempting
to bite
4 3 2 1
23. Inhibition/Hiding, staying
at the opposite side
4 3 2 1
Table 3: Behavioural assessment record: Observation sheet before / after blood pressure
measurement (duration 5 minutes)
Intern J Appl Res Vet Med • Vol. 13, No. 2, 2015. 131
changes (arithmetical and
relative) between groups at
each time point.
Statistical Methodology
Arithmetical changes were
analysed using a General-
ized Linear Model, includ-
ing factors group, sequence,
period, and animal within
sequence.
RESULTS AND DISCUSSION
The results of the study
showed a difference be-
tween the positive control
and Zenifel® at different
time points. At the rst
and third time points,
numerical differences were
noted between arithmeti-
cal changes for the two products. However,
the benet provided by Zenifel® for the
reduction in the stress index, in comparison
to the positive control, was not statistically
signicant at these points (p values 0.83 and
0.75 respectively). During the central stress-
ful event (blood pressure measurement)
Zenifel® provided a statistically signicant
reduction in the stress index compared to
the positive control (p=0.029). 4 to 5 hours
after the blood pressure measurement a very
small numerical difference was noted with-
out statistical signicance (p=0.74).
The differences of mean relative change
between the two products at each time
point are presented in Figure 1. The results
of this study, demonstrating a statistically
signicant reduction of the stress index with
Zenifel® when compared with the positive
control (Feliway®) in the situation of acute
stress, appear to support the hypothesis of
a synergistic or additive action between
nepetalactone and analogues of feline ap-
peasing pheromones. However, it is not
possible to dene whether this is due to an
interaction between two different sub-
stances, or whether nepetalactone stimulates
production of natural appeasing pheromones
by supranormal stimuli as has been previ-
ously speculated.4
The activity of nepetalactone seems to
be conned to olfactory stimulation in cats.13
Its effect in cats is not induced with systemic
or direct gastric administration, while the
anatomic positioning of the classical olfac-
tory system and pheromonal system in cats
are very close.1 Another important point sup-
porting stimulation of pheromone delivery is
the fact that until now, catnip responses have
never been seen in other species.4,14 The
specic nepetalactone response is limited
to Felidae sharing the same pheromonal
system.
Nepetalactone is a well-known intero-
mone acting as an attractant on cats or as a
repellent on various insect pests (mosqui-
toes, ticks, ies).21 On the other hand, it
is interesting to note that in this study the
signicant difference was noted during an
acute stress situation where the cats would
not have had the opportunity to deposit any
increase in pheromone production onto inan-
imate objects in the environment to appease
themselves. Until now, it has been believed
that fraction F4 of the facial pheromones
is required to improve interactions with
other living beings.1 It is, therefore, possible
that the combination of the F3 fraction and
Nepeta extract rich in nepetalactone could
have positive effects both in appeasement as
Figure 1: Zenifel®-induced proportional reduction in relative
stress index normalised on positive control (n=24 cats per
product)
Vol. 13, No.2, 2015 • Intern J Appl Res Vet Med.
132
derived from territorial pheromone mark-
ing and also in improving interactions with
human beings.
Despite very interesting results in the
situation of acute stress, no difference was
shown between the two products out-with
the period of manipulation.
Two reasons could possibly explain
this: a presumed relatively short duration
of action of nepetalactone15 or the fact
that the stressful event in this study, being
relatively short and of moderate intensity,
did not produce a signicant effect on cats
30-40 minutes later, nor 4 hours later. In the
authors’ opinion, the latter is the more likely
explanation. It should be noted additionally
that in order to obtain suitable behavioural
evaluation and acceptable levels of human
manipulation, all animals included in the
study were stable regarding behaviour and
had high initial wellbeing scores. This is not
always the case with cats in the eld, and
especially in in-clinic conditions. This could
possibly explain an absence of signicant
differences out-with the acute stress situa-
tion and represents one of the limitations of
the study. It is possible that less appeased
cats could have shown more variation in the
wellbeing/stress index. However it would
then have been almost impossible to form
homogeneous groups for the purposes of this
study.
The classical behavioural response
to nepetalactone has been reported to be
relatively short.15 However, less perceptible
effects such as calming, play-like behaviour,
and interaction stimulation seem to last
beyond the behavioural sequence called the
“catnip response”.2,20
A further potential limitation of this
study is the absence of a pure nepetalac-
tone group and the choice of Feliway® as
the positive control. Feliway® has already
been shown to be efcacious in the treat-
ment of moderate behavioural disorders3,8
and was thus judged to be acceptable as
a positive control. The use of plant-based
products containing cyclic lactones and able
to produce the “nepetalactone response” is
worldwide, and there is no need to prove
the existence of this response or describe
it. Nevertheless, this study design does
not permit us to conclude on whether the
benet of nepetalactone in association with
facial pheromones is additive or synergistic.
Beyond the number of groups or products
tested in the present study, the key limitation
was the fact that the behavioural evaluation
was done by human beings. In order to re-
duce this limitation, all staff involved in the
present trial were trained by a behavioural
specialist prior to animal manipulations. The
behavioural evaluations were performed
using a chart prepared by a specialist in
veterinary behaviour, and although these
questionnaires are not a standardized tool,
in behavioural medicine, such question-
naires are widely accepted.22,24 The number
of separate questions (measures) was high in
order to increase the robustness and objec-
tivity of the evaluation.25
The measurement of blood pressure
may have been an interesting parameter in
itself related to stress,26 and could potentially
have provided a less subjective indicator.
However, unless multiple measurements
are taken, the variability in this parameter
is too high to interpret the results, and there
is a large effect of habituation, which can
be seen when cats have multiple measure-
ments taken over time. In this study, the
idea was to use a non-invasive act which is
becoming routine in veterinary practice, but
which is known to be stressful to cats. The
cats were naïve to this procedure, and the
limited number of times it was performed
avoided any signicant effect of habituation.
If an alternative stress source was used, and
the cats were habituated to blood pressure
measurement, this may be an interesting
way to include a less subjective parameter
for a future study.
The action of nepetalactone is associ-
ated with a pleasurable emotional state in
domestic cats and other Felidae,4,15,19 but
without a clear behavioural consistency
between calming or euphorisant effects.15,19,20
Moreover, if the theory of reinforcement of
Intern J Appl Res Vet Med • Vol. 13, No. 2, 2015. 133
pheromone signalling is correct, it could be
suggested that nepetalactone may possibly
reinforce multiple feline pheromones, not
simply fraction F3.
During this study, no euphorisant effect
was reported. Rather, the results were much
more related to an overall better tolerance
of stress and tolerance of human interaction.
This is more desirable in practice and allows
targeted calming use of the nepetalactone
when it is given in association with the F3
fraction of the facial pheromones, which
provide an initial appeasing stimulus. This
conrms the interest of this association for
the management of moderate stress.
CONCLUSION
The association of the synthetic analogue
of the F3 fraction of the feline facial
pheromones and a Nepeta spp extract rich
in nepetalactone allows better management
of moderate acute stress in domestic cats
than analogues of feline facial pheromones
alone. Such an association could be a new
tool for the targeted management of moder-
ate behavioural disorders especially in the
case of acute stress. It could also possibly be
useful to facilitate adoption/socialisation of
kittens and to increase play-like behaviour
and social interaction.
Competing Interests and Funding
Disclosure
Authors NB, NC, PM, HG and DM are
employees of Virbac. Virbac paid for this
research which relates to a potential future
product in development.
Authors’ Contributions
NB, DM conceived the study. CB was
involved in the study protocol conception.
PM, HG were involved in the conception of
tested product. NB, NC, DM were respon-
sible for analysis and interpretation of the
data. NB, DM drafted the paper. All authors
contributed to critical revision of the paper
and approved the nal version.
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... In order to entice more cats to explore the F3 synthetic analogue, some have proposed pairing the analogue with another extract known to elicit a response in cats, catnip (Nepeta cataria). 37 Catnip is a preferred olfactory stimulus for cats and, in a recent study examining individual preferences, significantly more cats preferred a cloth impregnated with catnip compared with cloths with conspecific or gerbil scent. 38 As shown in Figure 4, several investigatory and other behaviors are associated with the catnip response, including sniffing, licking/chewing, chin/cheek rubbing, allorubbing and social rolling, and research indicates that about two-thirds of cats display this active response. ...
... Researchers examining the efficacy of pairing catnip with the F3 analogue compared a positive control of Feliway Classic with Zenifel (Virbac), an F3 analogue containing catnip extract. 37 The study was double-blind and each of the 24 study cats received both treatments; half of the cats received the Feliway Classic treatment first and the other half received the Zenifel treatment first. All cats were then switched to the other treatment. ...
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Practical relevance: Cats are one of the most common companion animals in the world. However, relatively little scientific research has been conducted on cat behavior. With problem behaviors a leading reason for relinquishment of cats to shelters, or abandonment outdoors, solutions to address feline behavioral problems can have important welfare benefits. Because naturally occurring pheromones produce measurable species-specific responses in cats, the use of synthetic pheromone products consisting of the same compounds may activate a specific behavioral response in the receiving individual, allowing humans to better communicate with cats and manage feline problem behavior. Aims: In this article the scientific background for naturally occurring feline pheromones and semiochemicals and their impact on cat behavior is reviewed. This is used as a foundation to explore the three feline synthetic pheromones currently available and the empirical evidence that exists for their effectiveness. From this information, several recommendations for veterinarians and behavior professionals on the application of feline pheromone therapy in the home and veterinary clinic setting are presented. Evidence base: The efficacy of synthetic pheromones as a tool for the management of problem behaviors is a relatively new area of research and only fairly recently has the need to implement more rigorous research methodology been recognized.
... Comportamiento: No se ha podido evidenciar científicamente el efecto relajante de la NC sobre los felinos (Bernachon et al, 2015). En un estudio se obtuvieron resultados positivos frente a situaciones de estrés específico en gatos. ...
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