Chiu S, Mishra R K
Naunyn Schmiedebergs Arch Pharmacol. 1980 Aug;313(1):45-50. doi: 10.1007/BF00505804.
In an attempt to elucidate the mechanism of d-lysergic acid diethylamide (LSD) induced catalepsy, the effects of cholinergic and dopaminergic agents, naloxone and L-propyl-leucyl-glycinamide (PLG) were studied in rats. The dose-dependent (50--500 micrograms kg-1 s.c.) and time-related cataleptic response elicited by LSD was preceded by a phase of hyperexcitability. The non-hallucinogenic analogue, 2-bromo-LSD (BOL), was without effect. Both apomorphine, the dopamine agonist, and L-DOPA antagonized LSD-induced catalepsy whereas the dopamine depleting agent alpha-methyl-p-tyrosine (alpha-MPT) slightly prolonged the cataleptic effect. Cholinergic muscarinic receptor stimulation with pilocarpine antagonized LSD-induced catalepsy. The muscarinic antagonists, atropine and scopolamine, intensified the hyperexcitable phase and potentiated the cataleptic effects of LSD. Nicotine slightly potentiated LSD action but mecamylamine antagonized it. While pre-treatment with naloxone, the narcotic antagonist and PLG prolonged the cataleptic response, post-treatment with naloxone effectively attenuated LSD-induced catalepsy. The behavioural data are interpreted to suggest that LSD-induced catalepsy may be mediated through diminished dopaminergic and cholinergic neuronal activity and under enkephalinergic modulation. The neuroanatomical foci and exact mechanism of action remain to be delineated.
为了阐明d-麦角酸二乙酰胺（LSD）诱发僵住症的机制，研究了胆碱能和多巴胺能药物、纳洛酮及L-丙基-亮氨酰-甘氨酰胺（PLG）对大鼠的影响。LSD引发的剂量依赖性（50 - 500微克/千克，皮下注射）和与时间相关的僵住症反应之前有一个过度兴奋期。非致幻类似物2-溴-LSD（BOL）没有效果。多巴胺激动剂阿扑吗啡和左旋多巴均拮抗LSD诱发的僵住症，而多巴胺耗竭剂α-甲基-对酪氨酸（α-MPT）则使僵住症效应稍有延长。毛果芸香碱刺激胆碱能毒蕈碱受体可拮抗LSD诱发的僵住症。毒蕈碱拮抗剂阿托品和东莨菪碱强化了过度兴奋期并增强了LSD的僵住症效应。尼古丁稍有增强LSD的作用，但美加明则拮抗其作用。虽然用麻醉拮抗剂纳洛酮和PLG预处理可延长僵住症反应，但用纳洛酮后处理可有效减弱LSD诱发的僵住症。行为学数据表明，LSD诱发的僵住症可能是通过多巴胺能和胆碱能神经元活动减弱以及脑啡肽能调节介导的。神经解剖学病灶和确切作用机制仍有待阐明。
