Di Ciano Patricia, Everitt Barry J
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
Neuropharmacology. 2004;47 Suppl 1:202-13. doi: 10.1016/j.neuropharm.2004.06.005.
Conditioned environmental stimuli are known to be important determinants of drug seeking. Traditional models of drug seeking under the control of conditioned stimuli have focused on the ability of conditioned reinforcers either to reinstate extinguished responding or to maintain prolonged chains of drug seeking under second-order schedules. These models have consistently suggested that it is the conditioned reinforcing, rather than other, effects of Pavlovian drug stimuli that most profoundly influence drug seeking. However, the impact of drug-associated conditioned reinforcers has not been studied directly and in isolation, not least because the instrumental seeking response is invariably the same as that which was previously reinforced with the drug itself. The purpose of the present study was, therefore, to investigate the conditioned reinforcing properties of drug-paired CSs using an acquisition of a new response procedure in which an animal learns to make a new instrumental response reinforced solely by the CS. It was found that CSs paired with either cocaine, heroin or sucrose supported the rapid acquisition of lever pressing for the CS that persisted over months of repeated, intermittent testing. Furthermore, rats did not acquire the lever press response when the CS was not paired with drug, suggesting that for this stimulus to acquire conditioned reinforcing properties, it must be predictively associated with the drug's effect. Moreover, lever pressing for the CS could not be explained as coincidental to an over-riding Pavlovian approach response to the location of the lever, since animals also acquired discriminated lever pressing when the CS was above the opposite, inactive lever. Extinction decreased responding with conditioned reinforcement, but only when the CS-US association was devalued prior to, and not after, acquisition of the lever press response, providing evidence for the establishment of habitual CS-maintained responding that may explain the persistence of drug-seeking responses in animal models of addiction and relapse.
已知条件性环境刺激是药物寻求行为的重要决定因素。在条件刺激控制下的传统药物寻求模型，重点关注条件强化物恢复消退反应的能力，或在二阶程序下维持长期药物寻求行为链的能力。这些模型一直表明，对药物寻求行为影响最为深远的是巴甫洛夫式药物刺激的条件强化作用，而非其他作用。然而，与药物相关的条件强化物的影响尚未得到直接且单独的研究，尤其是因为工具性寻求反应总是与之前用药物本身强化的反应相同。因此，本研究的目的是使用一种新反应习得程序来研究与药物配对的条件刺激的条件强化特性，在该程序中，动物学会做出仅由条件刺激强化的新工具性反应。研究发现，与可卡因、海洛因或蔗糖配对的条件刺激支持对条件刺激的杠杆按压反应的快速习得，这种反应在数月的重复间歇性测试中持续存在。此外，当条件刺激未与药物配对时，大鼠并未习得杠杆按压反应，这表明该刺激要获得条件强化特性，必须与药物的效果有预测性关联。此外，对条件刺激的杠杆按压反应不能解释为对杠杆位置的压倒性巴甫洛夫式趋近反应的巧合，因为当条件刺激位于相反的、不活动的杠杆上方时，动物也能习得辨别性杠杆按压反应。消退减少了条件强化的反应，但只有当条件刺激 - 无条件刺激的关联在杠杆按压反应习得之前而非之后被削弱时才会如此，这为习惯性条件刺激维持的反应的建立提供了证据，这可能解释了成瘾和复发动物模型中药物寻求反应的持续性。
