Fujikawa M, Yamada K, Nagashima M, Furukawa T
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
Pharmacol Biochem Behav. 1995 Mar;50(3):339-43. doi: 10.1016/0091-3057(94)00268-n.
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 micrograms/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 M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/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 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-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 mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 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 M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.
本研究旨在探讨β-肾上腺素能受体是否参与调节大鼠对催产素和α-黑素细胞刺激素(α-MSH)的哈欠反应。脑室内(ICV)注射剂量为50和100 ng/大鼠的催产素可引发哈欠。α-MSH(20微克/大鼠,ICV)不仅引发哈欠,还引发伸展和身体抖动。假定的毒蕈碱M1受体激动剂RS-86(2-乙基-8-甲基-2,8-二氮杂螺-(4,5)-癸烷-1,3-二酮氢溴酸盐),以100微克/大鼠的较低剂量ICV给药,以及以0.25-2.5 mg/kg的剂量皮下(SC)给药,也可引发哈欠。这些药物产生的哈欠反应通过腹腔内(IP)预先用β-肾上腺素能受体拮抗剂吲哚洛尔(20 mg/kg)预处理而显著增加,吲哚洛尔本身不会引发哈欠。催产素(50 ng/大鼠,ICV)加吲哚洛尔诱导的哈欠,但α-MSH(20微克/大鼠,ICV)或RS-86(0.5 mg/kg,SC)加吲哚洛尔诱导的哈欠不受催产素受体拮抗剂[d(CH2)5,Tyr(Me)2,Orn8]-血管加压素(100 ng/大鼠,ICV)的抑制。毒蕈碱受体拮抗剂东莨菪碱(0.5 mg/kg,SC)可抑制催产素、α-MSH或RS-86与吲哚洛尔联合给药诱导的哈欠,而多巴胺D2受体拮抗剂螺哌隆(0.5 mg/kg,SC)对此无影响。结果表明,神经肽催产素和α-MSH产生的哈欠与毒蕈碱M1受体激动剂产生的哈欠一样,受到β-肾上腺素能受体活性的抑制性调节,且涉及胆碱能激活,而非多巴胺能激活。