mise à jour du
30 novembre 2009
Prog europsychopharmacol Biol Psychiatry

Chronic nimodipine and yawning behavior
in grouped or individually housed rats
Fundaro A.
Institute of Pharmacology and Pharmacognosy
School of Pharmacy, University of Turin, Italy


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.

Yawning is a curious and still little understood behaviour which is displayed in many vertebrate species and is subject to a complex set of....
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.
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.
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.
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