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27 novembre 2005
Eur J Pharmacol
1986; 122; 2; 239-244
Antagonism of drug-induced yawning
and penile erections in rats
Gower AJ, Berendsen HH, Broekkamp CL
CNS Pharmacology Department, Oraganon, The Nederlands


A number of centrally active drugs were tested for antagonism of physostigmine- or apomorphine-induced yawning and for apomorphine-induced penile erections. The alpha 2-adrenoceptor antagonists piperoxan and idazoxan inhibited the yawning response without affecting the penile erections. The 5HT agonist quipazine and the histamine antagonist dexchlorpheniramine inhibited the yawning response more effectively than the penile erections. Dexchlorpheniramine even enhanced the apomorphine-induced penile erections and induced penile erections in physostigmine-treated rats. The 5HT antagonists metergoline and methysergide blocked the apomorphine-induced penile erections without affecting the yawning response. The alpha 2-adrenoceptor agonist clonidine, the dopamine antagonist sulpiride, the antihistaminic mepyramine and the benzodiazepine chlordiazepoxide inhibited both yawning and penile erections at the same dose level. The alpha1-adrenoceptor antagonists prazosin and phenoxybenzamine were inactive. It is concluded that yawning and penile erections can be differentially affected by drug treatments. Also, while concomitant yawning and penile erections can be selectively induced by a class of dopamine receptor agonists, the same selectivity does not apply to antagonism of these induced behaviours.
It was previously reported that yawning accompanied by an increase in penile erections, is chacteristically elicited by many dopamine agonists (Mogilnicka and Klimek, 1977; Benassi-Benelli et al., 1979), in particular those claimed to have selectivity for the dopamine autoreceptor (Gower et al., 1984). Cholinergic agents such as physostigmine also cause yawning but do not elicit penile erections (Urba-Holmgren et al., 1977; Gower et al., 1984). A cholinergic-dopaminergic interaction has been proposed to be involved in the mediation of yawning (Yamada and Furukawa, 1980; Gower et al., 1984; Ushijima et al., 1984). While both yawning and penile erections are similarly antagonized 1by centrally acting dopamine antagonists and anticholinergics, there is evidence that the two responses are differentially influenced by other centrally active drugs. For example, naloxone inhibits drug-induced yawning but enhances the penile erections elicited either by apomorphine (Berendsen and Gower, 1983) or by N-propylnorapomorphine (NPA) (Ferrari and Baggio, 1982). The first aim of this investigation was to obtain more evidence for the selective drug sensitivity of yawning and. penile erections. The second aim was to evaluate whether antagonism of the yawning-erection syndrome could be useful to identify drugs as antagonists for the receptors involved in the elicitation of these behavioural effects.
The present study shows that while drue induced yawning and penile erections have certain pharmacological attributes in common the responses could be separated in terms of the effects of pretreatment with certain antagonists. Thus the a2-adrenoceptor antagonists piperoxan idazoxan selectively inhibited yawning elicitec apomorphine or physostigmine but had no effect on apomorphine-induced penile erections. In contrast, the 5HT antagonists, metergoline methysergide selectively inhibited the penile erections without affecting yawning. These results report earlier work indicating an involvement different neuronal mechanisms in the two responses (Berendsen and Gower, 1983).
The effects of piperoxan and idazoxan imply role for the a2-adrenoceptor in the elaboration of yawning but not of penile erections. The reley a-adrenoceptor appears to be specifically a2 the alpha-antagonists prazosin and phenoxybe mine were without effect. This is not a straight ward involvement in the mediation of yawning since clonidine, at doses activating the a2-adrenoreceptor, did not itself elicit yawning (Gower et 1984) but reduced drug-induced yawning penile erections. The antagonism by clonidine penile erections, induced either by NPA or intraventricular ACTH, was also reported by Baggio and Ferrari (1980) and Poggioli et al. (19g
The antagonism of penile erections but yawning by methysergide and metergoline ports an exclusive role for serotonin in elaborating penile erections. Similar selective effect methysergide have already been described
Methygide blocked lisuride-induced penile erections did not affect either lisuride- or physos tigmine-induced yawning (Baggio and Ferrari 1983, Yamada and Furukawa, 1981). The involvement of serotonin cannot as yet be interpreted as a straightforward mediation by a serotonergic pathreway station between the dopamine receptors the penile erection response since quizapine a putative 5HT mimetic (Green et al. 1976, Roríguez et al., 1973) antagonized both yawning and penile erections. It may be that different serotonin receptors (Leysen et al., 1981) are involved in the elicitation and in the antagonism of penile erections. This is pertinent to the results of studies by Ahlenius and Larsson (1984) showing that 5-hydroxy-tryptophan depresses but the 5HT agonist, 8-hydroxy-2-(di-n-propyl)amino-tetralin, facilitates sexual behaviour.
The blockade by the atypical neuroleptic sulpiride of apomorphine-induced yawning while prostigmine-induced yawning was relatively unchanged confirms previous findings (Dubuc et al.,1982). It was found that sulpiride also blocked penile erections ad in this respect resembles the typical neuroleptic haloperidol (Benassi-Benelli et al. 1979; Berendsen and Gower, 1983).
The finding that dexchlorpheniramine induces penile erections is intriguing in view of the lack of such an effect with mepyramine. Both drugs have antihistamine effect in common. This observation is worth investigating further in view of both the on use of the two compounds in clinical practice and the interest in understanding the mechanism of action of induction of erections.
Mepyramine and dexchlorpheniramine and the anxiolytic chlordiazepoxide reduced drug-induced yawing. The sedative effects of these compounds may have interferenced with yawning. This is interesting because one might think that yawning is corollary of the sedation induced by apomorphine. It is also possible that these drugs interfere with the motor execution of the response. The effective dose of chlordiazepoxide also causes muscle relaxation.
These results therefore reveal drug-induced ing and penile erections as responses which influenced by psychotropic drugs with diverse mechanisms of action. Previously it has been demonstrated that the yawning-erection syndrome could be elicited by a group of dopamine agonists, suggesting selectivity for a receptor resembling the dopamine autoreceptor (Gower et al., 1984). Such selectivity cannot be claimed for the antagonism of yawning and erection syndrome and therefore caution is indicated when one is trying to use antagonism of apomorphine-induced yawning erections as an indication for blockade of the receptor resembling the dopamine autoreceptor.
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-Gower AJ, Berendsen HH, Broekkamp CL Antagonism of drug-induced yawning and penile erections in rats Eur J Pharmacol 1986; 122; 2; 239-244
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