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26 décembre 2002
Psychopharmacology (Berl) 1995;122(3):297-300
Effects of GABAergic drugs on physostigmine-induced yawning in rats
Zarrindast MR, Toloui V, Hashemi B
Department of pharmacology, school of medecine
Teheran University of medical sciences
Teheran Iran
Index de tous les travaux de MR Zarrindast


Yawning behaviour has been proposed to be associated with fatigue and recovery from stress (Barbizet 1985, Stoessl et al. 1987). The behaviour bas been the subject of very little empirical research.
The activation of central cholinergic and dopaminergic mechanisms bas been shown to induce yawning behaviour in rats (Urba-Holmgren et al. 1977; Zarrindast and Poursoltan 1989). Involvement of dopamine D2 receptors in yawning behaviour bas been proposed (Yamada et al. 1986). A central cholinergic mechanism has also been proposed to mediate the behaviour, and the yawning induced by dopamine agonists and agents acting on cholinoceptors is inhibited by muscarinic antagonists, such as scopolamine and atropine (Mogilnicka et al. 1984; Zarrindast and Poursoltan 1989). The paraventricular nucleus (Argiolas et al. 1987) and incerto-hypothalamic dopamine system (Melis et al. 1987) have been suggested to mediate yawning. Striatum is also one of the sites involved in yawning induced by drugs (Yamada et al. 1986).
The interaction between the GABAergic and dopaminergic and cholinergic systems within the striatum bas been studied (Scheel-Kruger and Arnt 1985). GABA-mimetic drugs have been shown to inhibit the release and turnover of striatal acetylcholine (Stoof et al. 1979; Scatton and Bartholini 1980, 1982), suggesting that the activation of striatal GABAergic receptors leads to the inhibition of striatal cholinergic neurons. Striatal cholinergic interneurons have been known to receive input from striatal GABA containing cell elements (DeBoer and Westerink 1994).
Our previous work showed that apomorphine-induced penile erection was influenced by GABAergic receptor agonists and antagonists (Zarrindast and Farahvash 1994). Since the GABAergic system may interact with cholinergic systems in brain, in the present study, the effects of GABA-A or GABA-B receptor agents on yawning induced by anticholinesterase physostigmine have been evaluated.
Discussion :
The present results show that intraperitoneal (IP) injection of the cholinesterase inhibitor physostigmine induced dose-dependent yawning. This is in agreement with previous reports that activation of cholinergic mechanism may induce yawning (Urba-Holmgren et al. 1977, Zarrindast and Poursoltan 1989; Zarrindast Jamshidzadeh 1992; Zarrindast et al. 1995). In this work, the influences of GABA-A and GABA-B receptors activation on physostigmine-induced yawning have been investigated. The inhibitory neurotransmitter GABA (DeFeudis 1977; Hosli and Hosli 1978; Johnston 1978) functions through specific GABA receptor sites. The GABA receptors in mammalian CNS have been divided into two different sites, termed GABA-A and GABA-B receptors (Bowery et al. 1980; Hill and Bowery 1981). GABA-A receptors are linked to chloride channels (Bowery 1982), while activation of GABA-B receptors reduces calcium currents (Desarmenien et al. 1984; Dunlop 1984).
Present data show that either the GABA-A receptor agonist muscimol (Bowery et al. 1984) or the GABA-B receptor agonist baclofen (Bowery et al. 1983, 1984) reduces yawning behaviour. Combination of both agonists produced an even stronger inhibitory effect. The response is a synergistic one. These results indicate that GABAergic system(s) may elicit a negative effect on physostigmine-induced yawning. The competitive GABA-A receptor antagonist bicuculline or the non-competitive GABA-A receptor antagonist picrotoxin (Ticku and Masky 1983) but not the GABAB receptor antagonist phaclofen (Kerr et al. 1987) decreased the inhibitory response of muscimol. In contrast, the response of baclofen was reduced by the GABA-B antagonist phaclofen but not by the GABAA antagonists. The data indicate that both GABA-A and GABA-B receptor stimulation may reduce cholinergic-induced yawning separately. Similarly, our previous work (Zarrindast and Farahvash 1994) showed that GABA-A or GABA-B receptor activation inhibited apomorphine-induced penile erection. The interaction between cholinergic and GABAergic neurons in the striatum, one of the possible sites for yawning, has been proposed (Stoof et al. 1979; Scatton and Bartholini 1980, 1982). Therefore, the existing data may support an interaction of the GABAergic and cholinergic systems for induction of yawning.
Administration of the GABA-A or GABA-B receptor antagonists can also reduce the yawning induced by physostigmine. The GABA-A antagonists bicuculline and picrotoxin may release GABA (Mitchell and Martin 1978). Since the antagonists can only block the pre-and postsynaptic GABA-A, but not the GABA-B receptors, stimulation of the postsynaptic GABA-B sites by released GABA may inhibit physostigmine-induced yawning.
The GABA-B autoreceptor has been shown to regulate the release of GABA (Bonanno et al. 1989). It may be possible that blockade of presynaptic GABAB receptors by phaclofen releases endogenous GABA and in turn, inhibits physostigmine-induced yawning through stimulation of GABA-A receptors.
Considering the inhibition of the release and turnover of the acetylcholine by GABA (Stoof et al. 1979; Scatton and Bartholini 1980, 1982), one may also speculate that the release of GABA by phaclofen decreases acetylcholine levels and inhibits physostigmine-induced yawning. The release of GABA by either the GABA-A receptor (bicuculline or picrotoxin) or the GABA-B receptor antagonist (phaclofen) may decrease yawning, while the combination of both antagonists may block both postsynaptic GABA-A and GABA-B receptors and thus abolish the response of both GABA antagonists.
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-Zarrindast MR, Toloui V, Hashemi B Effects of GABAergic drugs on physostigmine-induced yawning in rats; Psychopharmacology (Berl) 1995; 122; ; :297-300
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