Marinelli Peter W, Funk Douglas, Harding Stephen, Li Zhaoxia, Juzytsch Walter, Lê A D
Department of Neuroscience, Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Eur J Neurosci. 2009 Aug;30(4):671-8. doi: 10.1111/j.1460-9568.2009.06851.x. Epub 2009 Aug 3.
The aim of this study was to assess the effects of selective blockade of the delta (DOP) or mu (MOP) opioid receptors on alcohol-seeking induced by discrete cues and context. In Experiment 1, rats were trained to self-administer alcohol in an environment with distinct sensory properties. After extinction in a different context with separate sensory properties, rats were tested for context-induced renewal in the original context following treatment with the DOP receptor antagonist naltrindole (0-15 mg/kg, i.p.) or the MOP receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) (0-3 microg/4 microL, i.c.v.). In Experiment 2, reinstatement was tested with the presentation of a discrete light + tone cue previously associated with alcohol delivery, following extinction without the cue. The effects of naltrindole (0-5 mg/kg, i.p.) or CTOP (0-3 microg/4 microL, i.c.v.) were assessed. For context-induced renewal, 7.5 mg/kg naltrindole reduced responding without affecting locomotor activity. Both doses of CTOP attenuated responding in the first 15 min of the renewal test session; however, total responses did not differ at the end of the session. For discrete-cue-induced reinstatement, 1 and 5 mg/kg naltrindole attenuated responding but CTOP had no effect. We conclude that whereas DOP receptors mediate alcohol-seeking induced by discrete cues and context, MOP receptors may play a modest role only in context-induced renewal. These findings point to a differential involvement of opioid receptor subtypes in the effects of different kinds of conditioned stimuli on alcohol-seeking and support a more prominent role for DOP receptors.
本研究的目的是评估选择性阻断δ（DOP）或μ（MOP）阿片受体对由离散线索和环境诱导的觅酒行为的影响。在实验1中，训练大鼠在具有独特感官特性的环境中自行摄入酒精。在具有单独感官特性的不同环境中消退后，在用DOP受体拮抗剂纳曲吲哚（0 - 15毫克/千克，腹腔注射）或MOP受体拮抗剂D - Phe - Cys - Tyr - D - Trp - Orn - Thr - Pen - Thr - NH₂（CTOP）（0 - 3微克/4微升，脑室内注射）处理后，测试大鼠在原始环境中由环境诱导的恢复情况。在实验2中，在没有线索的消退后，通过呈现先前与酒精递送相关的离散光 + 音线索来测试复吸情况。评估了纳曲吲哚（0 - 5毫克/千克，腹腔注射）或CTOP（0 - 3微克/4微升，脑室内注射）的作用。对于环境诱导的恢复，7.5毫克/千克的纳曲吲哚减少了反应，但不影响运动活动。两种剂量的CTOP在恢复测试期的前15分钟内减弱了反应；然而，在测试期结束时总反应没有差异。对于离散线索诱导的复吸，1和5毫克/千克的纳曲吲哚减弱了反应，但CTOP没有效果。我们得出结论，虽然DOP受体介导由离散线索和环境诱导的觅酒行为，但MOP受体可能仅在环境诱导的恢复中起适度作用。这些发现表明阿片受体亚型在不同类型的条件刺激对觅酒行为的影响中存在差异参与，并支持DOP受体发挥更突出的作用。
