Institute of Pharmacology,
Università di Modena, Modena,
Italy
Introduction : It is well-known that
environment plays a crucial part in determining
animal behaviour; there is ample evidence that
social isolation, easily reproducible in
laboratory experiments, produces neurochemical,
anatomical and physiological alterations in
rodents. Isolated rats have been found to differ
from those reared in a community in their
sensitivity to the pharmacological effects of
drugs as determined by behavioural parameters;
moreover, marked changes in biogenic amine
dynamics have been demonstrated in their brains
and are probably connected with the observed
behavioural modifications.
The aim of the present study was to verify
some behavioural responses of isolated rats to
dopaminergic (DA) autoreceptorial doses of DA
agonists known to induce, in a dose-related
manner, various modifications in the behaviour
of rodents. The behavioural effects are: (1)
hypomotifity, penile erections (PE) and
stretching and yawning (SY), all attributable to
stimulation of DA D2 receptors and/or
presynaptic receptors (autoreceptors) which
cause a reduction in firing in DA cells and
inhibition of DA release; (2) stereotypies and
hypermotility involving DA postsynaptic
receptors.
In our experiments the drugs used as
pharmacological tools for the investigation of
PE and SY in isolated rats were
n-N-propylnorapomorphine (NPA) which is
typically active at low doses at
DA-autoreceptors and B-HT 920, an azepine
derivative regarded as a relatively selective
agonist at DA-autoreceptors. [...]
Discussion :
Disruption in the normal behaviour of
rodents after isolation has been widely
documented as has their altered sensitivity to
the action of various pharmacological drugs. Our
present findings indicate that isolation, though
neither extreme (olfactory and auditory
communication was maintained with other animals
in the same room) nor lengthy, is able to modify
some behavioural responses to autoreceptorial
doses of DA-agonists. While a reduction in PE
could be attributed to mechanisms different from
those specific to DA-systems, more intriguing is
the simultaneous reduction in SY.
Impaired spontaneous sexual behaviour has
already been reported after isolation, and
modified sex steroids have been detected in male
and female isolated rats. As Brain and Benton
point out, hormones may alter regional
concentrations of CNS neurotransmitters as well
as the activities of enzymes involved in their
metabolism. Also, evidence of changes in
catecholaminergic pathways hasbeen described by
several authors.
The hypothesis that reduced B-HT 920- and
NPA-induced PE and SY in rats might be ascribed
to some modification in DA-systems; is supported
by the reports of increased stereotypies induced
by amphetamine and amphetamine-like drugs and
enhanced tailpinch-induced oral behaviour in
isolated animals. In fact, it has been shown
that both behaviours are linked to DA system and
since, as previously mentioned, PE, SY and
stereotypies have been proposed as signs of
activation of different DA receptor subtypes,
their modification might be interpreted as being
due to altered sensitivity of the respective
receptors. This hypothesis is further supported
by the studies of Wilmot et al. who report
changes in the motor activity response to low
doses of apomorphine, suggestive of reduced
sensitivity of DA autoreceptors. However, since
the effect of any drug is dependent not only on
the specific site of action but also on other
factors, such as metabolism, transport and
disposition, the possibility that isolation may
affect these activities as well cannot be
excluded.
The above findings have broader
implications: since DA is one of the
neurotransmitters mainly involved in the control
and modulation of sexual behaviour, at least in
rats (all DA-agonists within a certain dosage
range not only stimulate PE in rats but also
have a potent effect on the mating of males and
lisuride, which acts on DA receptors, elicits
homosexual mounting), the question arises as to
whether expressions of sexual behaviour other
than PE are similarly influenced by differential
housing. If studies currently being undertaken
in our Institute prove this to be the case, then
isolation and behavioural signs viewed together
may afford valuable insight into the
neurochémical mechanisms underlying
certain forms of animal behaviour and the effect
of drugs.
