Effects of dorsal and ventral lateral hypothalamic lesions on voluntary alcohol consumption by rats.

Ventral lateral hypothalamic lesions, made before electrical stimulation, blocked the acquisition of a preference for alcohol by rats; but dorsal lateral hypothalamic lesions did not alter their alcohol consumption. Rats offered alcohol on alternate days, without stimulation, increased their alcohol intake but did not develop a stable preference for alcohol.

Suppression of ethanol intake following administration of dopamine-beta-hydroxylase inhibitors in rats.

A comparison was made between the efficacy of action of dopamine-beta-hydroxylase and/or aldehyde dehydrogenase inhibition in suppressing voluntary ethanol consumption in rats. Calcium carbimide, which caused the largest increase in blood acetaldehyde levels following ethanol injections, was the least effective in reducing ethanol consumption, whereas FLA-63, which had a smaller effect on blood acetaldehyde levels, was the most potent suppressor of ethanol ingestion. Disulfiram, which inhibits both aldehyde dehydrogenase and dopamine-beta-hydroxylase had an intermediate effect in terms of raising blood acetaldehyde levels and in suppressing ethanol intake. It is suggested that the inhibition of dopamine-beta-hydroxylase may be at least partly responsible for the suppression of ethanol intake seen following disulfiram administration, and that disruption of catecholamine synthesis may prove to be a more effective method for suppressing ethanol consumption.

Noradrenergic mediation of the positive reinforcing properties of ethanol: I. Suppression of ethanol consumption in laboratory rats following dopamine-beta-hydroxylase inhibition.

Ethanol-drinking rats were injected with the dopamine-beta-hydroxylase inhibitor FLA-57, prior to free-choice presentations of ethanol and water either for 5 alternate days (25 or 40 mg/kg i.p.) or for 5 consecutive days (45 mg/kg i.p.). In all cases, the FLA-57 treated animals markedly attenuated ethanol consumption while vehicle-injected controls showed no change from baseline. In the post-injection period ethanol intake gradually returned to baseline levels. Biochemical assays revealed that whole brain norepinephrine levels following injection of FLA-57 (15-60 mg/kg i.p.) were significantly depressed while dopamine and serotonin levels were slightly increased. It is suggested that norepinephrine may be involved in the mediation of the positive reinforcing properties of ethanol regulating its self-administration.

Noradrenergic mediation of the positive reinforcing properties of ethanol: II. Extinction of ethanol-drinking behavior in laboratory rats by inhibition of dopamine-beta-hydroxylase. Implications for treatment procedures in human alcoholics.

Following stabilization of consumption of a 15% (v/v) ethanol solution in a free-choice with water, rats were presented with a forced-choice of ethanol for 10 consecutive alternate days. Prior to each forced-choice presentation experimental animals were injected with the non-toxic dopamine-beta-hydroxylase inhibitor FLA-57 (30 mg/kg i.p.) while control animals received only vehicle injections. At the termination of the injection phase when ethanol was again made available in a free-choice with water, ethanol consumption for the FLA-57 treated animals was markedly suppressed. These data are interpreted in terms of extinction resulting from the procedure whereby performance of the ethanol drinking response was perpetuated by force with the pharmacological reinforcing properties being blocked by FLA-57-induced depletions of norepinephrine. Applications of these procedures in the treatment of human alcoholics are discussed.