D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats
D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats
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DOI：
10.1007/s00213-002-1305-x
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Neisewander, JL
中科院分区：
文献类型：
--
作者：
Alleweireldt, AT;Kirschner, KF;Neisewander, JL
原理……多巴胺D1受体拮抗剂和激动剂都能减弱由可卡因引发物或与可卡因配对的刺激所引发的寻求可卡因的行为（即，在没有可卡因强化的情况下的操作性反应）。目前尚不清楚这些效应是否由D1受体介导。
目的……本研究测试D1拮抗剂（SCH - 23390）是否会逆转D1激动剂（SKF - 81297）对寻求可卡因行为的减弱效应，以及这些效应是否涉及行为干扰。
方法……经过训练的大鼠为了获得可卡因强化而按压杠杆，同时伴有与每次注射配对的光和声音提示，它们每天接受消退训练，在此期间反应没有预定的结果（即，既没有可卡因，也没有与可卡因配对的刺激复合物）。在反应减弱之后，研究了D1拮抗剂对D1激动剂通过反应相依性提示呈现或可卡因引发来恢复寻求可卡因行为的剂量 - 反应函数的影响。一个单独的实验评估了激动剂对拮抗剂用于提示恢复的剂量 - 反应函数的影响。在每个测试阶段还测量了刻板行为和活动。
结果……共同施用SCH - 23390可逆转SKF - 81297在可卡因引发的恢复过程中对寻求可卡因行为的减弱效应。然而，即使在同一测试阶段共同施用这两种药物可逆转激动剂诱导的刻板行为和拮抗剂诱导的活动减退，但没有发现提示恢复过程中减弱效应被逆转的证据。
结论……研究结果表明，在可卡因恢复过程中，D1受体药物对寻求可卡因行为的减弱效应是由多巴胺D1受体介导的；然而，目前尚不清楚在提示恢复过程中这些药物对寻求可卡因行为的效应是否由D1受体介导。不过，很明显这些药物对寻求可卡因行为的减弱并非仅仅由于行为干扰。
Rationale.. Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. Objectives.. The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. Methods.. Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. Results.. The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. Conclusions.. The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.