Quinlan Matthew G, Sharf Ruth, Lee David Y, Wise Roy A, Ranaldi Robert
Department of Psychology, Queens College, CUNY, 65-30 Kissena Boulevard, Flushing, NY 11367, USA.
Psychopharmacology (Berl). 2004 Aug;175(1):53-9. doi: 10.1007/s00213-003-1771-9. Epub 2004 Feb 7.
We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)--not usually considered part of reward circuitry--might have similar effects.
To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine.
Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 microg/0.5 microl into the SN and 8 were tested with injections of 0 microg or 4 microg/0.5 microl into a site 2 mm dorsal to the SN site.
Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding.
These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug's ability to elevate dopamine levels in the nucleus accumbens.
我们最近发现，阻断腹侧被盖区的多巴胺D1型受体可降低静脉注射可卡因的奖赏效应；在此，我们探讨了阻断相邻黑质（SN）（通常不被认为是奖赏回路的一部分）中的D1受体可能具有类似效应的可能性。
检验黑质中多巴胺D1受体阻断可降低可卡因奖赏效应的假说。
给21只大鼠植入静脉导管和双侧引导套管，以便能直接向黑质或黑质背侧注射。训练大鼠按照固定比率1（FR1）强化程序自行静脉注射可卡因（每次注射1.0mg/kg）。在形成稳定反应后，13只动物在双侧微量注射剂量为0、1、2或4μg/0.5μl的SCH 23390预处理后进行测试，8只动物在向黑质部位背侧2mm处注射0μg或4μg/0.5μl进行测试。
向黑质微量注射SCH 而向黑质背侧注射对反应无显著影响。
这些数据表明，阻断黑质中树突释放的多巴胺可降低可卡因的奖赏效应。这些发现补充了越来越多的证据，即可卡因的奖赏效应并不局限于该药物提高伏隔核中多巴胺水平的能力。
