mise à jour du
22 août 2002
Psychopharmacology 1988; 95; 34--37
 Multifocal sites of action involved in dopaminergic-cholinergic neuronal interactions in yawning
Itsuko Ushijima, Yasushi Mizuki, and Michio Yamada
Department of Neuropsychiatry, Yamaguchi University, School of Medicine, Ube Japan
Bromocriptine (BRQ, a dopamine D-2 receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a muscarinic cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 2.5 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively.

BRC-induced yawning was inhibited by high doses of SK&F38393 (5 and 10 mg/kg), a selective D-1 receptor agonist. BRC or SK&F38393 alone did not induced stereotyped behaviors. However, when BRC was administered after SK&F38393 (5.0 and 10 mg/kg), stereotyped behaviors occurred; i.e., mainly sniffing at 2.5 and 5.0 mg/kg BRC, and mainly licking and biting 10 and 20 mg/kg BRC.

A high dose of apomorphine (4 mg/kg IP) completely inhibited physostigmine-induced yawning (physostigmine yawning) but did not affect pilocarpine-induced yawning (pilocarpine yawning). BRC (2.5-20 mg/kg) increased physostigmine yawning in an additive fashion.

Pilocarpine yawning was completely blocked by either low or high doses of BRC. The inhibitory effect of BRC on pilocarpine yawning was reversed by sulpiride (20 mg/kg). oc-Methyl-p-tyrosine (aMPT; 100 and 200 mg/kg) did not affect physostigmine yawning but diminished pilocarpine yawning. Furthermore, physostigmine (0.2 mg/kg) inhibited apomorphine (4.0 rng/ kg)-induced hyperlocomotion and sniffing but not licking and biting, whereas pilocarpine (4.0 mg/kg) had the opposite effect.

These results suggest that activation of postsynaptic dopamine receptors (primarily D-1 receptors) may inhibit cholinergic neurons activated by cholinesterase inhibition, i.e., endogenous acetylcholine, and that the postsynaptic sensitivity of cholinergic neurons to a direct acetylcholine agonist (muscarinic M-1 receptor agonist) may be reduced by stimulation of presynaptic dopamine receptors (D-2 receptor) and/or inhibition of dopamine synthesis.

Bromocriptine (BRC), a selective dopamine D-2 receptor agonist, has been reported to evoke yawning in rats (Protais et al. 1983). Similarly, cholinomimetic drugs and low doses of apomorphine, a non-selective dopamine receptor agonist. also induce yawning (Urba-Holmgren et al. 1977; Yamada and Furjikawa 1980, 1981). Yawning induced by apomorphine, physostigmine or pilocarpine is inhibited by scopolamine, a muscarinic receptor blocking agent, but not by methylscopolamine, a peripheral anticholinergic agent or by mecamylamine, a nicotinic receptor blocking agent.

This suggests involvement of central muscarinic receptors (UrbaHolmgren et al. 1977; Yamada and Furukawa 1980. 1981) but not central nicotinic receptors (Ushijima et al. 1985) in mediating yawning behavior. In addition, since low doses of haloperidol inhibit apomorphine-induced yawning, it is possible that this behavior may be mediated by cholinergie activation secondary to the inhibition of dopamine transmission (Yamada and Furukawa 1980: Ushijima et al. 1985). Furthermore, there is evidence suggesting that acetylcholine release is controlled by the dopamine D-2 receptor (Closse et al. 1985). Physostigmine-induced yawning is potentiated by fluphenazine, a long-acting neuroleptic, but is inhibited by higher doses of apomorphine, whereas pilocarpine-induced yawning is not affected by either drug, suggesting that the sensitivity of cholinergie neurons to a cholinesterase inhibitor, physostigmine, but not to a direct acetylcholine agonist, pilocarpine, may be altered in the dopaminergie-cholinergic neuronal interactions. However, reserpine, a catecholamine depletor, activates apomorphine-, physostigmine- and pilocarpine-induced yawning (Yamada and Furukawa 1980). The present studies were designed to clarify dopaminergic-cholinergic mechanisms involved in mediating drug-induced yawning responses.

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