resolutionmini

 

 

 

haut de page

 

 

 

 

 

 

 

 

 

mise à jour du
23 janvier 2003
Pharmacol Biochem Behav
1981; 15; 711-715
lexique
Serotonergic and dopaminergic effects
on yawning in the cat
James L. Marini
Department of Psychiairy, Yale University School of Medicine
Urba-Holmgren R, Holmgren B Serotonergic modulation of yawning

Chat-logomini
Recent pharmacological studies of yawning in the rat have shown that in this species the behavior is affected by cholinergic, dopaminergic, and serotonergic agents, and to some extent by glutamate. The cholinergic drugs physostigmine and pilocarpine (PILO) elicit yawning by a mechanism involving muscarinic, but not nicotinic, cholinergic receptors in the central nervous system. The frequency of such cholinergically-elicited yawning is greatest in rats less than 10 days of age. There is also evidence that a doparninergic mechanism inhibits yawning in the rat. For instance, fluphenazine, which blocks dopamine (DA) receptors, potentiates physostigmine-induced yawning, and yawning is induced by doses of the DA agonist, apomorphine (APO), that inhibit dopamine-firing. It has been proposed that cholinergic activation and dopaminergic inhibition act concomitantly in the expression of yawning in rats.

A serotonergic mechanism also affects the behavior, although it has been less thoroughly studied. For example, citalopram, an inhibitor of serotonin (5HT) reuptake, strongly potentiates physostigmine-induced yawning in rats, and the effect of citalopram is antagonized by metergoline, which blocks 5HT receptors. Because administration of citalopram alone was without effect on yawning, the action of 5HT was assumed to be "modulatory", that is, to require ongoing (cholinergic?) activity or tone for its expression. This proposal is consistent wilh the results of studies of the application of 5HT to motor neurons in anesthetized rats and cats, and to neurons in the myenteric plexus of the guinea pig, all of which indicate a modulatory effect of 5HT on neuronal activity in these systems.

Hallucinogens with 5HT-agonist properties, including d-lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DNIT), have also been reported to modulate motor neuron activity. DMT elicits yawning in monkeys, and these and other LSD-like hallucinogens have been reported to produce increased frequencies of yawning in cats; data on this subject have been published only for the 5HT agonist 5-methoxy-N,N-dimethyltryptamine.

During studies of the specificity of a cat behavior model for hallucinogens, I observed that LSD elicited a high frequency of yawning. Since LSD is a potent serotonergic agent which also possesses dopaminergic properties, and since both 5HT and DA have been implicated in yawning, I used LSD-eliciled yawning as a starting point for a study of the roles of serotonergic and dopaminergic mechanisms in the behavior. In addition to its relevance to the pharmacology of yawning and the behavioral pharmacology of LSD, the study was intended as a preliminary investigation of yawning as a behavioral index of serotonergic and dopaminergic properties of drugs. Since 5HT mechanisms appear to increase, and DA mechanisms decrease, the frequency of occurrence of yawning, drug-elicited yawning may provide a simple system for studying the interactions of serotonergic and dopaminergic drugs, or for investigating the concomitant expression of 5HT- and DA-related properties of a drug with -mixedeffects. For purposes of comparison, I also scored limb flicking, a well-studied feline behavior which is not obviously related to yawning, and is elicited by many drugs, including LSD and related hallucinogens. [...]

 
As mentioned in the introduction, serotonin appears to play a role in yawning in several species. Hallucinogenic 5HT agonists have been reported to elicit yawning in the cat, and the present work shows that, in addition to limb flicking, LSD reliably elicits a significantly increased frequency of yawning. LSD has been much studied in the cat with respect to its elicitation of limb flicking, in which behavior 5HT mechanisms are important. In an earlier study it was shown that pretreatment of cats with methysergide, which blocks some types of 5HT receptors, significantly antagonized both yawning and limb flicking elicited by LSD in cats, and moreover, that methysergide produced cross tolerance to both of these behaviors when it was administered 24 hr before LSD. Taken together, these results provide consistent evidence that yawning has a serotonergic comportent in the cat, and that LSD-elicited yawning involves a serotonergic mechanism.

Unlike the case of the cat, LSD-like hallucinogens do not appear to elicit yawning in the rat. For example, doses of 0.025 or 0.10 mg/kg of LSD (subcutaneously) do not elicit yawning in hooded rats, and LSD, 5-methoxy-N,N-dimethyltryptamine, and similar agents do not do so at doses producing marked effects on acoustic startle in albino rats. The recent literature on the serotonin syndrome following LSD and similar agents in the rat does not report yawning as a sign or side effect of hallucinogen treatment.

Like LSD, LIS has potent serotonomimetic properties and elicits limb flicking in the cat; LIS-elicited limb flicking is also antagonized by methysergide. However, the present work shows that LIS does not elicit yawning, demonstrating that serotonomimetic potency is not a sufficient condition for drug-induced yawning. LIS appears to have more potent dopamine agonist properties than LSD. By analogy with the work in the rat showing inhibition of yawning by a DA mechanism, the frequencies of yawning aller LSD and LIS may be hypothesized to reflect both 5HT-mediated facilitation and DA-mediated inhibition, with the latter effect predominating in the case of LIS, the more potent doparninergic agent. This hypothesis is supported by the results of the LSD + LIS experiment, since LIS appeared to reduce the frequency of LSD-elicited yawning. Since combining LSD and LIS did not reduce the occurrence of limb flicks, the drugs interaction with respect to yawning is relatively specific.

The hypothesis was directly tested by using the DA agonist, APO.The 1.0 mg/kg APO dose significantly reduced LSD-elicited yawning, as would be expected from stimulation of DA receptors that immediate inhibition of yawning. The elicitation of yawning by 0.256 mg/kg of the DA-receptor blocking agent, HAL, is also consistent with the hypothesis. However, the hypothesis cannot explain why a higher HAL dose did not increase yawning. The result with HAL at 0.256 mg/kg may therefore reflect a statistical artifact, or the intervention of a mechanism unaccounted for by the simple hypothesis. Reversal of HAL-elicited yawning by LIS is consistent with the hypothesis, but must be interpreted cautiously given the preceding remarks.

Although a dose of 1 mg/kg of PILO increased yawning in infant rats, it had no effect on yawning in the cats used in these studies. In the rat, the maximum effect of PILO was seen at 2-4 mg/kg, doses I did not employ in cats because of the drug's pronounced parasympathornimetic activity. APO has been reported to elicit a significantly increased frequency of limb flicking in cats at doses of 2 and 4 mg/kg when animals are observed in a scoring chamber, but I did not find uniformly increased limb flicking at similar doses (1.6 and 3.2 mg/kg). Since the enviromnent in which cats are observed has been shown to affect their responses to at least some drugs, and since I scored cats in their home cages, the difference in scoring enviromnent may explain the different observations after high APO doses.

The results of this study show that limb flicking and yawning have different behavioral pharmacologies in the cat, and that the frequency of limb flicking elicited by LSD is insensitive to DA agonists. They also suggest that serotonerigic facilitation and dopaminergic inhibition can act concomitantly in the expression of drug-elicited yawning in the cat. If this proves to be the case, it would provide a useful system for studying such interactions.