Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol.

The effect of the i.p. administration of ethanol on the release of dopamine (DA) and on the output of its main metabolites, dihydroxyphenylacetic acid and homovanillic acid, was estimated in the rat by transcerebral dialysis of two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of ethanol (0.25-0.5 g/kg i.p.) stimulated DA release specifically in the n. accumbens and elicited pure behavioral stimulation. Higher doses of ethanol (1.0-2.5 g/kg) elicited sedation and hypnosis and stimulated further DA release and dihydroxyphenylacetic acid and homovanillic acid output in the accumbens and, although less, also in the caudate. High doses of ethanol (5 g/kg i.p.) elicited long-lasting hypnosis and sedation and induced a depression followed by stimulation of DA release in the accumbens. DA release in the caudate was stimulated further. Low doses of apomorphine (0.05 mg/kg s.c.) reversed completely the stimulant effect of 0.5 g/kg of ethanol on behavior and on DA release in the accumbens. Moreover, the stimulation of behavior and of DA release in the accumbens elicited by 0.5 g/kg of ethanol were abolished completely by pretreatment with 700 mg/kg of gamma-butyrolactone, an agent which blocks DA firing and DA release. The results indicate that ethanol preferentially stimulates DA transmission in the mesolimbic system probably by activating the firing activity of mesolimbic DA neurons and provide direct evidence that these changes are involved in the motor stimulant effects of ethanol.