Marusich Julie A, Branch Marc N
University of Florida, Department of Psychology, USA.
Exp Clin Psychopharmacol. 2009 Aug;17(4):266-82. doi: 10.1037/a0016682.
Previous research with rats and monkeys has shown that tolerance to behavioral effects of cocaine developed if the drug was administered before behavioral test sessions but not if it was administered after sessions, a finding known as contingent tolerance. In contrast, a recent experiment using pigeons found that they showed tolerance resulting from postsession drug administration (noncontingent tolerance). The 4 experiments reported in this article were conducted to examine that result more fully. Experiment 1 found that immediate presession administration of cocaine to pigeons reliably led to tolerance to effects on food-reinforced operant key pecking and that immediate postsession administration of cocaine also led to tolerance in half the subjects, those whose key pecking was not suppressed by postsession dosing. Experiment 2 showed that eating in the home cage under the effects of postsession cocaine was not necessary for tolerance to develop to effects of postsession cocaine and that the majority of subjects developed tolerance from postsession cocaine administration. Experiment 3 found that mere drug exposure in the home cage without exposure to an experimental session did not reliably produce tolerance during the behavioral session. Experiment 4 showed that tolerance from postsession cocaine administration could be observed even when daily dosing was discontinued during dose-response curve assessment. Therefore, the combined results showed that pigeons often developed tolerance to effects of cocaine during the behavioral session when cocaine was administered postsession and that this tolerance was not the result of feeding under effects of the drug.
先前对大鼠和猴子的研究表明,如果在行为测试环节之前给药,会产生对可卡因行为效应的耐受性,但如果在测试环节之后给药则不会产生,这一发现被称为条件耐受性。相比之下,最近一项以鸽子为对象的实验发现,它们在测试环节之后给药会产生耐受性(非条件耐受性)。本文所报告的4项实验旨在更全面地检验这一结果。实验1发现,对鸽子在测试环节之前立即给予可卡因能可靠地使其对食物强化的操作性啄键行为效应产生耐受性,并且在测试环节之后立即给予可卡因也会使一半的受试对象产生耐受性,即那些啄键行为未被测试环节后给药所抑制的受试对象。实验2表明,在测试环节后可卡因作用下于饲养笼中进食并非产生对测试环节后可卡因效应耐受性的必要条件,并且大多数受试对象在测试环节后给予可卡因时产生了耐受性。实验3发现,仅在饲养笼中接触药物而不接触实验环节并不能在行为测试环节可靠地产生耐受性。实验4表明,即使在剂量反应曲线评估期间停止每日给药,仍可观察到测试环节后给予可卡因产生的耐受性。因此,综合结果表明,当在测试环节后给予可卡因时,鸽子在行为测试环节中经常会对可卡因效应产生耐受性,并且这种耐受性并非药物作用下进食的结果。