Blaha C D, Phillips A G, Lane R F
Regul Pept. 1987 Jun;17(6):301-10. doi: 10.1016/0167-0115(87)90053-x.
In vivo electrochemical techniques were used to study the effects of the sulfated (CCK8-S) and unsulfated (CCK8-US) forms of cholecystokinin octapeptide on apomorphine-induced inhibition of dopamine (DA) release in the nucleus accumbens of the anesthetized rat. A dose-dependent inhibition of DA release was observed with intravenous (i.v.) injections of apomorphine. CCK8-S administered i.v. at the nadir of the apomorphine-induced inhibition of DA release produced a transient and dose-dependent increase followed by a prolonged decrease in DA release CCK8-US was ineffective in altering apomorphine's inhibitory effects on DA release. The CCK receptor antagonist proglumide injected i.v. 10 min after apomorphine administration had no effect on apomorphine-induced inhibition of DA release, but blocked the effects of CCK8-S on this inhibition. Given that apomorphine may inhibit DA release by a direct hyperpolarizing action on DA neurons, the observation that CCK8-S temporarily reverses apomorphine-induced effects and further inhibits DA release suggests that CCK8-S exerts its inhibitory effects via a process of depolarization block in DA neurons. These findings indicate that apomorphine and CCK8-S may inhibit DA release in vivo by opposite effects on DA cell membrane potentials and suggest that endogenously released CCK may serve to modulate mesolimbic DA neurotransmission.
采用体内电化学技术研究了硫酸化八肽胆囊收缩素（CCK8-S）和未硫酸化八肽胆囊收缩素（CCK8-US）对阿扑吗啡诱导的麻醉大鼠伏隔核多巴胺（DA）释放抑制作用的影响。静脉注射阿扑吗啡可观察到DA释放呈剂量依赖性抑制。在阿扑吗啡诱导的DA释放抑制最低点静脉注射CCK8-S，可使DA释放产生短暂的剂量依赖性增加，随后出现长时间降低；CCK8-US对改变阿扑吗啡对DA释放的抑制作用无效。在阿扑吗啡给药10分钟后静脉注射CCK受体拮抗剂丙谷胺，对阿扑吗啡诱导的DA释放抑制无影响，但可阻断CCK8-S对该抑制作用的影响。鉴于阿扑吗啡可能通过对DA神经元的直接超极化作用抑制DA释放，CCK8-S能暂时逆转阿扑吗啡诱导的效应并进一步抑制DA释放这一观察结果表明，CCK8-S通过DA神经元的去极化阻滞过程发挥其抑制作用。这些发现表明，阿扑吗啡和CCK8-S可能通过对DA细胞膜电位的相反作用在体内抑制DA释放，并提示内源性释放的CCK可能参与调节中脑边缘DA神经传递。
