Sorge Robert E, Stewart Jane
Department of Psychology, Center for Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Pharmacol Biochem Behav. 2006 Jun;84(2):300-5. doi: 10.1016/j.pbb.2006.05.013. Epub 2006 Jun 27.
We have previously shown that chronic treatment with the partial mu-opioid receptor agonist, buprenorphine, blocks the nucleus accumbens dopamine response to an acute injection of heroin, whereas it potentiates the response to an acute injection of cocaine after 4-5 days of treatment. Here we studied the effects of chronic exposure to buprenorphine via osmotic minipumps for up to 28 days (1.5 or 3.0 mg/kg/day) on responses to acute injections of heroin and cocaine. Increases in locomotion induced by heroin (0.25 mg/kg, sc), given on the 5th, 15th or 25th day of treatment were unaffected by buprenorphine, whereas increases induced by cocaine (20 mg/kg, ip) were enhanced early in treatment but not on the 15th or 25th days. Using in vivo microdialysis we found that both the suppression of the dopaminergic response in the nucleus accumbens to heroin and the potentiation to cocaine seen early in treatment diminished over the 26-27 days, whereas basal dopamine levels remained elevated throughout. Therefore, although these studies do not explain the mechanism whereby buprenorphine reduces heroin and cocaine intake, they do indicate that there is little tolerance to the presence of chronic buprenorphine.
我们之前已经表明，用部分μ-阿片受体激动剂丁丙诺啡进行长期治疗，会阻断伏隔核多巴胺对海洛因急性注射的反应，而在治疗4 - 5天后，它会增强对可卡因急性注射的反应。在此，我们研究了通过渗透微型泵对丁丙诺啡进行长达28天（1.5或3.0毫克/千克/天）的长期暴露对海洛因和可卡因急性注射反应的影响。在治疗的第5天、第15天或第25天给予海洛因（0.25毫克/千克，皮下注射）所诱导的运动增加不受丁丙诺啡影响，而可卡因（20毫克/千克，腹腔注射）所诱导的运动增加在治疗早期增强，但在第15天或第25天没有增强。通过体内微透析我们发现，在治疗早期观察到的伏隔核中多巴胺能反应对海洛因的抑制以及对可卡因的增强作用在26 - 27天内逐渐减弱，而基础多巴胺水平在整个过程中仍保持升高。因此，尽管这些研究没有解释丁丙诺啡减少海洛因和可卡因摄入量的机制，但它们确实表明对慢性丁丙诺啡的存在几乎没有耐受性。
