Progressive effects of cocaine on behavior and central amine metabolism in rhesus monkeys: relationship to kindling and psychosis.
Progressive effects of cocaine on behavior and central amine metabolism in rhesus monkeys: relationship to kindling and psychosis.
复制标题
可卡因对恒河猴行为和中枢胺代谢的渐进影响：与点燃和精神病的关系。
作者：
R. Post;Kopanda Rt;Black Ke
恒河猴长期服用相同剂量的可卡因长达 6 个月，与病理行为的逐渐改变和癫痫发作的易感性增加有关。猴子最初表现出明显的过度活跃刻板反应长达两个月，开始表现出越来越多的抑制行为，包括僵住、运动抑制以及异常的视觉跟踪和凝视。长期服用可卡因 10 周后，13 只动物中的 4 只出现了越来越严重的舌颊运动障碍。动物最初对给定剂量的可卡因没有表现出惊厥，最终在相同剂量的可卡因中出现惊厥，然后在随后的注射后表现出惊厥频率增加。在兴奋性刻板综合征和抑制性综合征期间，脑脊液中多巴胺代谢物高香草酸（HVA）的水平显着升高；丙磺舒给药后 HVA 也观察到类似的趋势。在急性可卡因给药后，只有丙磺舒诱导的血清素代谢物 5-羟基吲哚乙酸的积累显着升高。抽搐、运动障碍和抑制综合征的逐渐增加似乎与血浆或脑脊液中可卡因峰值水平的变化无关，并且建议使用药理学点燃模型作为数据的替代解释。该研究通过强调行为和神经后遗症的渐进性改变，扩展了目前兴奋剂诱发的精神病模型，并表明这种渐进机制在人类精神病的发展中也可能很重要。
Chronic administration of the same dose of cocaine to rhesus monkeys for up to 6 months was associated with progressive alterations in pathological behavior and increased susceptibility to seizures. Monkeys initially displaying prominent hyperactive stereotypic responses for up to 2 months began to demonstrate increasing amounts of inhibitory behavior, consisting of catalepsy, motor inhibition, and abnormal visual tracking and staring. Four of 13 animals developed increasing intensities of lingual-buccal dyskinesias after 10 weeks of chronic cocaine. Animals initially showing no convulsions to a given dose of cocaine eventually developed convulsions to the same dose, and then displayed an increased frequency of convulsions following subsequent injections. Levels of the dopamine metabolite, homovanillic acid (HVA), in the cisternal cerebrospinal fluid were significantly elevated during both excitatory stereotypic and inhibitory syndromes; a similar trend was observed for HVA after probenecid administration. Only the probenecid-induced accumulations of the serotonin metabolite 5-hydroxyindoleacetic acid, following acute cocaine administration, were significantly elevated. The progressive increases in convulsions, dyskinesias, and the inhibitory syndrome did not appear related to alterations in peak levels of cocaine in plasma or CSF, and a pharmacological kindling model is suggested as an alternate explanation of the data. The study extends the current models of stimulant-induced psychoses by highlighting the progressive alterations in behavior and neurological sequelae and in suggesting that this progressive mechanism may also be important in the development of psychosis in man.