Picker M.J.
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
Behav Pharmacol. 1989;1(2):141-152.
The effects of the neuroleptic compounds clozapine, chlorpromazine and haloperidol were examined alone and in combination with the muscarinic cholinergic agonist oxotremorine in pigeons responding under a fixed-consecutive-number schedule. Under this procedure, nine or more consecutive responses on one response key followed by a single response on a second response key produced 3sec access to grain. In one component of this schedule (FCN 9-SD), an external discriminative stimulus was presented following the completion of the response requirement on the first response key, whereas no stimulus change was programmed in the other component (FCN 9). When administered alone, clozapine (0.1-5.6mg/kg) and chlorpromazine (3.0-170mg/kg) decreased accuracy (i.e. increased the mean number of response runs per reinforcer) under the FCN 9 at doses that had no effect under the FCN 9-SD. In contrast, haloperidol (0.03-1.7mg/kg) and oxotremorine (0.001-0.1mg/kg) had no effect on accuracy under either variant of the FCN schedule. Under both variants of the FCN schedule, clozapine, chlorpromazine, haloperidol and oxotremorine produced dose-related decreases in rates of responding. When administered in combination, oxotremorine (0.01 and 0.03mg/kg) antagonized the accuracy- and response rate-decreasing effects of both clozapine and chlorpromazine. Although neither haloperidol or oxotremorine decreased accuracy when administered alone, these drugs produced large decreases in accuracy when administered in combination. In most instances, the magnitude of these decreases in accuracy was larger than those obtained following the administration of clozapine or chlorpromazine. The effects of the co-administration of oxotremorine and haloperidol on rate of responding were generally additive. These findings indicate that both the accuracy- and response rate-decreasing effects of clozapine and chlorpromazine are, in part, mediated by their antagonist actions at muscarinic cholinergic receptors. In addition, the finding that the co-administration of haloperidol and oxotremorine decreased accuracy provides support at the behavioral level for an interaction of the dopaminergic and cholinergic systems.
在固定连续数强化程序下对鸽子进行实验，研究了抗精神病药物氯氮平、氯丙嗪和氟哌啶醇单独使用以及与毒蕈碱型胆碱能激动剂氧化震颤素联合使用时的效果。在此程序中，在一个反应键上连续做出九个或更多反应，然后在第二个反应键上做出一次反应，可获得3秒的谷物获取时间。在此强化程序的一个部分（FCN 9-SD）中，在第一个反应键上完成反应要求后会呈现一个外部辨别性刺激，而在另一个部分（FCN 9）中则未设置刺激变化。单独给药时，氯氮平（0.1 - 5.6mg/kg）和氯丙嗪（3.0 - 170mg/kg）在FCN 9条件下会降低准确性（即增加每次强化物的平均反应次数），而在FCN 9-SD条件下无此作用剂量。相比之下，氟哌啶醇（0.03 - 1.7mg/kg）和氧化震颤素（0.001 - 0.1mg/kg）在FCN强化程序的任何一种变体下对准确性均无影响。在FCN强化程序的两种变体下，氯氮平、氯丙嗪、氟哌啶醇和氧化震颤素均产生与剂量相关的反应率降低。联合给药时，氧化震颤素（0.01和0.03mg/kg）拮抗了氯氮平和氯丙嗪对准确性和反应率的降低作用。虽然氟哌啶醇和氧化震颤素单独给药时均未降低准确性，但联合给药时会大幅降低准确性。在大多数情况下，这些准确性降低的幅度大于氯氮平或氯丙嗪给药后的降幅。氧化震颤素和氟哌啶醇联合给药对反应率的影响通常是相加的。这些发现表明，氯氮平和氯丙嗪对准确性和反应率的降低作用部分是由它们对毒蕈碱型胆碱能受体的拮抗作用介导的。此外，氟哌啶醇和氧化震颤素联合给药降低准确性的发现为多巴胺能系统和胆碱能系统的相互作用提供了行为水平的支持。
