Sills T L, Onalaja A O, Crawley J N
Section on Behavioural Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892-1380, USA.
Eur J Neurosci. 1998 May;10(5):1895-902. doi: 10.1046/j.1460-9568.1998.00201.x.
Individual differences within strains of rats have been demonstrated for dopamine-mediated behaviours and responses to dopaminergic drugs. Differences in mesolimbic dopamine function may underlie individual differences in some of these behaviours, including sugar consumption and amphetamine hyperlocomotion. The present study addressed two potential mechanisms for these differences in dopamine-mediated behaviours. The possibility of functional differences in dopamine receptor subtypes was tested in LOW and HIGH sugar feeders. LOW and HIGH feeders did not differ in their response to the partial D1 agonist SKF-38393. The highest dose (2.5 mg/kg) of the D2 agonist quinpirole stimulated locomotor activity to a greater degree in a subset of HIGH sugar feeders as compared with LOW feeders. All doses of amphetamine induced a greater locomotor response in HIGH feeders as compared with LOW feeders, and HIGH feeders exhibited higher levels of extracellular dopamine in the nucleus accumbens than LOW feeders following exposure to sugar and treatment with amphetamine. These results support the interpretation that LOW and HIGH feeders exhibit differences in presynaptic nucleus accumbens dopamine function that account for the expression of individual differences in sugar consumption and response to amphetamine treatments. A subset of HIGH feeders may also exhibit greater D2 receptor function.
大鼠品系内的个体差异已在多巴胺介导的行为以及对多巴胺能药物的反应中得到证实。中脑边缘多巴胺功能的差异可能是这些行为中某些个体差异的基础,包括糖分消耗和苯丙胺引起的运动亢进。本研究探讨了多巴胺介导行为中这些差异的两种潜在机制。在低糖摄入者和高糖摄入者中测试了多巴胺受体亚型功能差异的可能性。低糖摄入者和高糖摄入者对部分D1激动剂SKF - 38393的反应没有差异。与低糖摄入者相比,D2激动剂喹吡罗的最高剂量(2.5毫克/千克)在一部分高糖摄入者中对运动活性的刺激程度更大。与低糖摄入者相比,所有剂量的苯丙胺在高糖摄入者中诱导的运动反应更大,并且在接触糖和接受苯丙胺治疗后,高糖摄入者伏隔核中的细胞外多巴胺水平高于低糖摄入者。这些结果支持这样的解释,即低糖摄入者和高糖摄入者在伏隔核突触前多巴胺功能上存在差异,这解释了糖分消耗和对苯丙胺治疗反应的个体差异的表现。一部分高糖摄入者也可能表现出更强的D2受体功能。