Effect of dorsal raphe injections of the GABAA agonist, muscimol, on ethanol intake and measures of intoxication in Wistar rats.

Abstract

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.