1. The effects of a chronic administration
(around 30 mg/ kg/day) of the dihydropyridine
calcium antagonist nimodipine, on apomorphine
induced yawning behaviour of grouped or
individual housed rats, were studied.
2. Nimodipine treatment had no effect in
grouped rats.
3. Individually housed animals gave a
significant lower number of yawns in respect to
grouped controls: this difference disappeared in
isolated, nimodipine treated, group.
4. The results show the ability of
nimodipine to restore a depressed behavioural
performance.
Introduction
Yawning is a curious and still little
understood behaviour which is displayed in many
vertebrate species and is subject to a complex
set of....
Drugs
Nimodipine was dissolved in a minimal amount
of ethanol and subsequently diluted in water
containing 0.5 methylcellulose in order to
obtain a stable suspension. Treated groups drank
water in which nimodipine was suspended (0.4
mg/ml), control groups drank water prepared as
for treated groups but without nimodipine. The
suspension was put in graduated black bottles
(to protect nimodipine from light effects) and
freshly renewed every day. The dose of
nimodipine was calculated from the total
quantity of the solution drunk in the period of
the experiment (thirty days), taking into
account the number of rats and their average
weight. No differences were observed in food
(around 20 g/rat/day) and water intake (25-30
ml/rat/day) between control and treated groups
in grouped and isolated animals. The average
dose of nimodipine was 30 mg/kg/day.
Discussion
The oral route, the chronic administration
and the dose of nimodipine used, tried to
simulate as much as possible the clinical use of
the drug. Nimodipine treatment did not cause, in
grouped rats, a significant difference in the
yawns number. Apomorphine-induced yawning is
potentiated by acute administration of some
dihydropyridine calcium channel blockers
(Bourson and Moser 1990) The discrepancy in our
research could be due to some experimental
differences (nimodipine dose, rats age, etc.)
and to the fact that the administration was
chronic. During chronic administration,
modification on neurotransmitter systems could
have overcome by adaptive mechanisms.
According to Greco and Baenjuinger (1991)
yawning is likely in situations where arousal is
low, but in which there is some reason to remain
awake and alert. The function of yawning would
be to increase arousal which is
correlated with serotonin concentration in
the limbic system (Egan et al. 1979). The most
consistent finding concerning putative
neurotransmitters and isolation is a decrease in
cerebral serotonin turnover (Valzelli and
Bernasconi 1979) Individual housing could have
lowered the yawn's frequency modifying the
activity of arousal system.
The significant lower pattern of yawnings
found in isolated rats was brought up to grouped
controls performance by the nimodipine
treatment.
As the dihydropirydine compounds in
behavioural tests of dopaminergic activity
(Bourson et al 1989) affected apomorphine
induced yawning but not penile erection, and did
not affect amphetamine-induced rotation or drug
discrimination, it seems unlikly that they act
on yawning behaviour affecting dopamine release.
An increased serotoninergic tone is reported
during dihydropyridine compounds administration
(Colado et al. 1991; Gaggi et al. 1992) and
serotonin is reported to play an excitatory
influence in the regulation of yawning (Marini
1981; Urba-Holmgren et al. 1979) As a working
hypothesis it thus seems possible that
nimodipine restored the depressed yawn's
behaviour by suppressing at least part of the
activity of arousal system.
Conclusion
Our results seem to confirm the nimodipine
ability to restore a normal behavioural pattern
if depressed by a stressing situation such as a
prolonged isolation and appeared to substantiate
the usefulness of nimodipine to treat some
disorders of the central nervous system.
-Argiolas A
et al Role of calcium in the expression of
ACTH-induced stretching, yawning and penile
erection Brain Research Bulletin 1990; 24;
853-856
-Argiolas
A, Melis MR Oxytocin-induced penile erection
and yawning: role of calcium and prostaglandins
Pharmacol Biochem Behav 1990; 35; 3;
601-605
-Czyrak A et
al. Some central pharmacological effects of
the calcium channel antagonist flunarizine J
Neural Transm 1991;83:179-188
