Nader Michael A, Sinnott Rachna S, Mach Robert H, Morgan Drake
Department of Physiology and Pharmacology, The Center for Neurobiological Investigation of Drug Abuse, Wake Forest University School of Medicine, 5th Floor NRC, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
Psychopharmacology (Berl). 2002 Oct;163(3-4):292-301. doi: 10.1007/s00213-002-1202-3. Epub 2002 Aug 29.
Environmental context has been shown to influence responding under multiple schedules of food reinforcement and to modify the behavioral effects of drugs. However, no systematic study has been conducted under conditions of cocaine self-administration. The hypothesis was that changes in the magnitude of food reinforcement would affect cocaine-maintained response rates and influence the behavioral potency of a dopamine antagonist to decrease cocaine self-administration.
A multiple schedule was used to evaluate the effects of changes in the magnitude of food reinforcement on the self-administration cocaine dose-response curve and on the behavioral potency of a dopamine receptor antagonist to decrease food- and cocaine-maintained responding.
Rhesus monkeys (n=3) were trained to self-administer intravenous cocaine under a multiple fixed-interval (FI) 5-min schedule of food and cocaine presentation. Food (one or four pellets) was available in the first and third components and cocaine (saline, 0.01-0.3 mg/kg per injection) was available in the second and fourth components. After completion of cocaine dose-response curves, the effects of the dopamine D(2)/D(3) receptor antagonist 2,3-dimethoxy-N-(9-p-fluorobenzyl)-azabicyclo[3.3.1]nonan-3beta-yl benzamide (MABN) were examined.
Cocaine- and food-maintained responding varied as a function of dose and were characterized as inverted U-shaped functions; cocaine-maintained response rates were significantly influenced by the magnitude of food in the other component. The behavioral potency of MABN on food- and cocaine-maintained responding was not influenced by the magnitude of food reinforcement.
These results suggest that cocaine self-administration under a multiple schedule with food reinforcement is influenced by the environmental context. These schedule interactions, however, did not alter the behavioral effects of a dopamine D(2)/D(3) receptor antagonist.
环境背景已被证明会影响在多种食物强化时间表下的反应,并改变药物的行为效应。然而,尚未在可卡因自我给药的条件下进行系统研究。假设是食物强化量的变化会影响可卡因维持的反应率,并影响多巴胺拮抗剂降低可卡因自我给药的行为效力。
采用多重时间表来评估食物强化量的变化对可卡因自我给药剂量反应曲线以及多巴胺受体拮抗剂降低食物和可卡因维持反应的行为效力的影响。
恒河猴(n = 3)接受训练,在食物和可卡因呈现的多重固定间隔(FI)5分钟时间表下自我静脉注射可卡因。在第一和第三部分可获得食物(一粒或四粒食丸),在第二和第四部分可获得可卡因(盐水,每次注射0.01 - 0.3毫克/千克)。完成可卡因剂量反应曲线后,检查多巴胺D(2)/D(3)受体拮抗剂2,3 - 二甲氧基 - N - (9 - 对氟苄基) - 氮杂双环[3.3.1]壬烷 - 3β - 基苯甲酰胺(MABN)的作用。
可卡因和食物维持的反应随剂量而变化,其特征为倒U形函数;可卡因维持的反应率受到另一部分食物量的显著影响。MABN对食物和可卡因维持反应的行为效力不受食物强化量的影响。
这些结果表明,在有食物强化的多重时间表下可卡因自我给药受环境背景影响。然而,这些时间表相互作用并未改变多巴胺D(2)/D(3)受体拮抗剂的行为效应。