Gerrits M A, Ramsey N F, Wolterink G, van Ree J M
Rudolf Magnus Institute, Department of Pharmacology, University of Utrecht, The Netherlands.
Psychopharmacology (Berl). 1994 Apr;114(3):486-94. doi: 10.1007/BF02249340.
The involvement of dopamine D1 receptor systems in the reinforcing properties of opiate reward was studied by examining the effect of the dopamine D1 antagonist SCH23390 on the initiation of heroin self-administration in rats. The D1 antagonist was administered daily systemically or locally in the nucleus accumbens (NAC), after which the animals were allowed to self-administer heroin (IV) in a 3-h session for 5 consecutive days. Systemic treatment with SCH23390 (0.17 and 0.5 mg.kg-1) significantly decreased heroin intake during initiation of heroin self-administration, while a dose of 0.06 mg.kg-1 was not effective. Local administration of SCH23390 (0.5 and 2.5 micrograms/site) in the NAC did not affect heroin intake. Both systemic and intra-accumbal administration of SCH23390 dose dependently decreased motor behavior measured in a small open field. The attenuation of heroin intake during initiation of heroin self-administration by blockade of dopamine D1 receptor systems may be due to a decrease in the reinforcing effects of heroin or more likely to a reduction in non-reinforcement-related behavior. The dopamine D1 receptors present in the NAC are probably not involved in opiate reward.
通过研究多巴胺D1拮抗剂SCH23390对大鼠海洛因自我给药起始的影响，探讨了多巴胺D1受体系统在阿片类奖赏强化特性中的作用。多巴胺D1拮抗剂每日全身给药或局部注射于伏隔核（NAC），之后让动物在3小时内进行海洛因（静脉注射）自我给药，连续5天。用SCH23390（0.17和0.5mg·kg-1）进行全身治疗，在海洛因自我给药起始阶段显著降低了海洛因摄入量，而0.06mg·kg-1的剂量则无效。在NAC局部注射SCH23390（0.5和2.5微克/位点）不影响海洛因摄入量。全身给药和伏隔核内给药SCH23390均剂量依赖性地降低了在小开放场中测量的运动行为。在海洛因自我给药起始阶段，通过阻断多巴胺D1受体系统来减少海洛因摄入量，可能是由于海洛因强化作用的降低，或者更可能是由于与非强化相关行为的减少。存在于NAC中的多巴胺D1受体可能不参与阿片类奖赏。
