Department of Psychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
J Psychopharmacol. 1993 Jan;7(1 Suppl):43-51. doi: 10.1177/026988119300700108.
The discriminative stimulus effects of the nicotine antagonist mecamylamine have been investigated to characterize further its behavioural effects and its interactions with (-)-nicotine. Rats were trained to discriminate the effects of mecamylamine from saline in a two-bar operant conditioning procedure with food reinforcers presented on a tandem schedule of reinforcement. Mecamylamine (3.5 mg/kg s.c.) acquired strong stimulus control over behaviour and there was only a small reduction in overall rates of responding. The mecamylamine stimulus generalized completely to some ganglion-blocking drugs (order of relative potency: pentolinium > mecamylamine > pempidine) but it did not generalize to other ganglion-blockers (hexamethonium, trimetaphan and chlorisondamine). The mecamylamine stimulus also failed to generalize to (-)-nicotine, to muscarinic antagonists (atropine and scopolamine) or to excitatory amino acid antagonists (dizocilpine, phencyclidine and D-CPPene). Mecamylamine, pempidine, hexamethonium, trimetaphan, (-)-nicotine, scopolamine, phencyclidine, dizocilpine and D-CPPene were tested up to doses that reduced overall rates of responding. Tests also showed that (-)-nicotine did not antagonize the response to mecamylamine. The discriminative stimulus produced by mecamylamine may originate at nicotinic receptors but whether these are located centrally or peripherally is unclear. There was no evidence that either muscarinic or excitatory amino acid receptors were involved in mediating the effect.
美加明作为烟碱拮抗剂的辨别刺激效应已被研究，以进一步描述其行为效应及其与（-）-烟碱的相互作用。大鼠在双杠操作性条件反射程序中接受食物强化，以串联强化程序辨别美加明与生理盐水的作用。美加明（3.5mg/kg sc）对行为具有很强的刺激控制作用，整体反应率仅略有下降。美加明的刺激完全泛化到一些神经节阻滞剂（相对效力顺序：戊烷咪 > 美加明 > 派迷清），但不会泛化到其他神经节阻滞剂（六烃季铵、三甲噻吩和氯桑定）。美加明的刺激也不会泛化到（-）-烟碱、毒蕈碱拮抗剂（阿托品和东莨菪碱）或兴奋性氨基酸拮抗剂（地卓西平、苯环己哌啶和 D-CPPene）。美加明、派迷清、六烃季铵、三甲噻吩、（-）-烟碱、东莨菪碱、苯环己哌啶、地卓西平和 D-CPPene 的测试剂量达到了降低整体反应率的水平。测试还表明，（-）-烟碱不能拮抗美加明的反应。美加明产生的辨别刺激可能起源于烟碱受体，但这些受体是位于中枢还是外周尚不清楚。没有证据表明毒蕈碱或兴奋性氨基酸受体参与介导这种作用。
