mise à jour du
22 juillet 2004
Naunyn-Schmiedebergs'Arch Pharmacol
1987; 335; 667-672
Relation between yawning behavior and
central serotonergic neural system in rats
S Okuyama, H Shimamura, S Hashimoto, H Aihara
Research center, Saitama, Japan


Introduction : Yawning behavior elicited by low doses of apomorphine is attributed to stimulation of the inhibitory presynaptic dopamine (DA) autoreceptors. Physostigmine also elicits yawning. Apomorphine elicited yawning can be reduced by pretreatment with the muscarinic antagonist scopolamine while physostigmine elicited yawning can be enhanced by pretreatment with the neuroleptics spiperone spiroperidol, haloperidol and fluphenazine. It has been proposed that dopaminergic and cholinergic related factors may interact to, elicit yawning behavior. Moreover, a dopaminergic-cholinergic link is recognized in the striatum. DA receptors are localized on the striatal acetylcholine (ACh) neurons and an inhibitory dopaminergic input may influence the cholinergic system of the striatum. Electrophysiological evidence confirmed that the nigrostriatal dopaminergic neurons inhibit the striatal and cholinergi neurons.
Serotonin (5-HT) is also present in relatively high concentrations in the striatum of the rat. The origin of 5HT fibres in the striatum is the dorsal raphe. Evidence obtained from electrophysiological studies showed that 5-HT acts as an inhibitory transmitter. Olpe and Koella (1977) have shown that stimulation of the dorsal raphe neurons has a potent inhibitory action on striatal neurons. Davis and Tongroach (1978) demonstrated that the inhibition of striatal neuronal firing produced by stimulation of the dorsal raphe nucleus could be mimicked by the iontophoretic application of 5-HT in the striatum and that both effects were antagonized by methysergide, a drug which blocks the postsynaptic 5-HT receptors. Similarly, biochemical studies indicated that there are inhibitory 5-HT receptors located on terminals of dopaminergic neurons in the striatum. Therefore, yawning elicited by apomorphine and/or physostigmine is probably affected by changes in serotonergic neuronal activities. However, yawning behavior and serotonergic functions have not been extensively studied. In the present study, the possible influence of 5-HT on druginduced yawning in rats was investigated.
Discussion : Apomorphine and physostigmine cause yawning in rats, in a biphasic manner, ie., low, but not high, doses produce yawning behavior. The peak effects of apomorphine and physostigmine were observed with a dose of 0.1 mg/kg, s.c. of each drug. This observation was in good accord with the data in the literature.
Apomorphine elicited yawning was reduced following pretreatment with the 5-HT precursor, 5-HTP, but was enhanced by pretreatment with the 5-HT synthesis inhibitor p-CPA or the serotonergic neurotoxin 5,7-DHT. These findings indicate that apomorphine elicited yawning is enhanced by decreases in serotonergic-related neuronal activity and reduced by increases in such neuronal activity.
Ennis et al. (1981) reported that inhibitory 5-HT receptors are reported on the terminals of the dopaminergic neuron in the located. DA release is inhibited not only by DA but also, by 5-HT in striatal slices. In addition, the excitatory behavior noted when DA receptors are stimulated can be mimicked or enhanced by p-CPA pretreatment, 5,7-DHT pretreatment, raphe nucleus lesion and attenuation of 5-HT receptor stimulation. Likewise, lesioning of the
raphe which reduces 5-HT levels in the forebrain causes a significant increase in the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC). Thus, the inhibitory effects of 5-HT seem to be mediated via 5-HT receptors at the DA nerve terminals. Actually, apomorphine enhanced WDS induced by 5-HTP. WDS induced by 5-HTP may involve the activation of serotonergic neuron activity. Apomorphine, in a low dose, elicited only yawning in control rats, whereas the same dose elicited stereotypy in rats pretreated with higher doses of p-CPA.
Marini (1981) reported that serotonergic activation and dopaminergic inhibition can act concomitantly in the expression of drug-elicited yawning in cats. Unlike the findings in cats, potent serotomimetic drugs (LSD-like hallucinogens) do not appear to elicit yawning in rats, These observations suggested that the behavioral pharmacology of yawning differs between these species. In the present experiments, 5-HTP pretreated rats never showed yawning behavior.
Physostigmine-elicited yawning was reduced by pretreatment with 5-HTP. However, physostigmine-elicited yawning was not affected by pretreatment with p-CPA and 5,7-DHT. These observations are difficult to reconcile with those of Urba-Holmgren et al. (1978) who found that yawning induced by physostigmine was enhanced by Lu 10-171, a selective 5-HT uptake inhibitor, which, by itself does not induce yawning. This effect was counteracted by metergoline which blocks 5-HT postsynaptic receptors. Although we have not precise explanation for this difference, experimental conditions and the age of the rats may play some role.
Microinjecting apomorphine directly into, the striatum elicited yawning behavior, with a bell-shaped dose response curve. Stereotypy was also observed when the highest dose of apomorphine was given. Intrastriatal microinjection of physostiginine had no effect on behavior. These findings indicate that the site of action of apomorphine differs from that of physostigmine. Dourish et al. (1985) suggested that a cholinergic-dopaminergig linked system in the striatum was involved in the induction of yawning. However, our results did not support this hypothesis because (i) physostigrnine elicited yawning was not affected by pretreatinent with p-CPA and 5,7-DHT, (ii) direct microinjection of physostigmine into the striatum did not elicit yawning.
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