INVOLVEMENT OF BETA-ADRENOCEPTORS IN REGULATION OF THE YAWNING INDUCED BY NEUROPEPTIDES, OXYTOCIN AND ALPHA-MELANOCYTE-STIMULATING HORMONE, IN RATS

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 mu g/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M(1) receptor agonist, administered ICV at a lower dose of 100 mu g/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 mu g/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)(5),Tyr(Me)(2),Orn(8)]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a muscarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D-2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M(1) receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.