Tomkins D M, Sellers E M, Fletcher P J
Addiction Research Foundation, Toronto, Ontario, Canada.
Alcohol Alcohol Suppl. 1994;2:551-8.
Peripheral administration of selective agents for GABAA receptors have been reported to modify ethanol self-administration behaviour. Recently, it has been reported that the dorsal and median raphe may represent potential brain sites for mediating these effects since injection of the GABAA agonist, muscimol, into these sites increased ethanol intake. The aim of the present study was to extend these findings and assess the effect of muscimol, injected into either the dorsal or median raphe, on a range of parameters including ethanol intake, ethanol-induced hypothermia and ethanol-induced suppression of high rates of responding. Wistar rats trained to drink 12% ethanol for 40 mins each day, increased their ethanol consumption, but not water consumption, following injection of 50 ng muscimol into the dorsal raphe. Ethanol intakes returned to baseline levels the day following drug treatment. The same dose injected into the median raphe has been shown to produce a non-selective increase in both water and ethanol intake. Further analysis of this data revealed that the rats tended to avoid the ethanol solution on the day following treatment. A further difference between the dorsal and median raphe was revealed in the ethanol-induced hypothermia experiment. Thus, 10 ng muscimol injected into the median raphe potentiated the hypothermic response induced by intraperitoneal injection of 1.5 g/kg ethanol, whereas injection into the dorsal raphe had no significant effect on this measure. Intraperitoneal injection of 0.5 g/kg ethanol suppressed operant responding for water intake and this behaviour was not altered by dorsal raphe injection of muscimol. Together these results suggest that GABAergic mechanisms within the dorsal raphe represent an important neural site for controlling the ingestion of ethanol, but not that of ethanol intoxication.
据报道，对外周给予GABAA受体选择性药物可改变乙醇自我给药行为。最近，有报道称中缝背核和中缝正中核可能是介导这些效应的潜在脑区，因为向这些脑区注射GABAA激动剂蝇蕈醇会增加乙醇摄入量。本研究的目的是扩展这些发现，并评估向中缝背核或中缝正中核注射蝇蕈醇对一系列参数的影响，包括乙醇摄入量、乙醇诱导的体温过低以及乙醇诱导的高反应率抑制。每天训练40分钟饮用12%乙醇的Wistar大鼠，在向中缝背核注射50纳克蝇蕈醇后，其乙醇消耗量增加，但水消耗量未增加。药物治疗后的第二天，乙醇摄入量恢复到基线水平。已证明，向中缝正中核注射相同剂量会使水和乙醇摄入量均非选择性增加。对这些数据的进一步分析表明，大鼠在治疗后的当天倾向于避开乙醇溶液。在乙醇诱导的体温过低实验中，还揭示了中缝背核和中缝正中核之间的另一个差异。因此，向中缝正中核注射10纳克蝇蕈醇可增强腹腔注射1.5克/千克乙醇诱导的体温过低反应，而向中缝背核注射则对该指标无显著影响。腹腔注射0.5克/千克乙醇会抑制水摄入的操作性反应，而中缝背核注射蝇蕈醇不会改变这种行为。这些结果共同表明，中缝背核内的GABA能机制是控制乙醇摄入的重要神经位点，但不是控制乙醇中毒的位点。
