LACK OF INVOLVEMENT OF DELTA-OPIOID RECEPTORS IN MEDIATING THE REWARDING EFFECTS OF COCAINE
LACK OF INVOLVEMENT OF DELTA-OPIOID RECEPTORS IN MEDIATING THE REWARDING EFFECTS OF COCAINE
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DOI：
10.1007/bf02245816
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发表时间：
1995-08-01
影响因子：
3.4
通讯作者：
SHIPPENBERG, TS
中科院分区：
文献类型：
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作者：
DEVRIES, TJ;BABOVICVUKSANOVIC, D;SHIPPENBERG, TS
据报道，非选择性阿片类拮抗剂纳洛酮和部分激动剂丁丙诺啡可减少人类和恒河猴的可卡因自我给药（SA）和复发。最近还提出了一些数据，表明δ-阿片受体参与调节可卡因的条件奖励效应。鉴于这些发现，本SA和位置条件反射的研究进行了检查的影响，选择性δ阿片受体拮抗剂纳曲吲哚后可卡因的奖励作用。训练Sprague-Dawley大鼠按照FR 2强化时间表自我给予可卡因（每次输注1.0 mg/kg）。一旦达到稳定的可卡因SA速率，就开始剂量反应和拮抗剂试验。对于拮抗剂测试，大鼠在2小时SA阶段开始前30分钟接受纳曲吲哚（0.03-10.0 mg/kg，IP）。然后确定响应于可卡因递送（每次输注0.25和1.0 mg/kg）的SA行为。纳曲吲哚剂量为0.03-3.0 mg/kg时，未改变大鼠接受的可卡因输注次数。较高剂量的纳曲吲哚（10.0 mg/kg），这显着抑制自发活动，导致可卡因（0.25 mg/kg/输注）SA行为减少16%。当终止SA疗程并重复给予纳曲吲哚（1.0 mg/kg）3天时，未观察到可卡因SA再获得的改变。位置条件反射研究也未能发现纳曲吲哚（0.1-3.0 mg/kg）对可卡因（10 mg/kg）诱导的条件性位置偏好的影响。纳曲吲哚，本身，并没有引起显着的地方空调。这些数据未能表明δ-阿片受体在调节可卡因的正性强化或条件性奖励效应中的作用。此外，他们认为纳洛酮、纳洛酮和丁丙诺啡对可卡因SA行为的治疗作用可能不是由δ阿片受体的特异性阻断引起的。
The non-selective opioid antagonist naltrexone and the partial agonist buprenorphine have been reported to reduce cocaine self-administration (SA) and relapse in both humans and rhesus monkeys. Data suggesting an involvement of delta-opioid receptors in modulating the conditioned rewarding effects of cocaine were also recently presented. In view of such findings, the present SA and place conditioning studies were conducted to examine the influence of the selective delta-opioid receptor antagonist naltrindole upon the rewarding effects of cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg per infusion) on an FR2 schedule of reinforcement, Dose-response and antagonist testing commenced once stable rates of cocaine SA were achieved. For antagonist testing, rats received naltrindole (0.03-10.0 mg/kg, IP) 30 min prior to the start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and 1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03-3.0 mg/kg did not alter the number of cocaine infusions taken by the rats. A higher dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity, resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior. When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were seen. Place conditioning studies also failed to find an effect of naltrindole (0.1-3.0 mg/kg) on cocaine (10 mg/kg) - induced conditioned place preferences. Naltrindole, by itself, did not induce significant place conditioning. These data fail to indicate a role of delta-opioid receptors in modulating either the positive reinforcing or conditioned rewarding effects of cocaine. Furthermore, they suggest that the therapeutic actions of naloxone, naltrexone and buprenorphine on cocaine SA behavior may not result from the specific blockade of delta-opioid receptors.