Enhancement of amphetamine- and cocaine-induced locomotor activity after chronic ethanol administration.

The effects of amphetamine and cocaine on locomotor activity in mice were studied after 3 weeks of chronic administration of ethanol by liquid diet. When testing was started 24 h after cessation of the ethanol treatment, no differences were seen on the first administration between the effects of the psychostimulants in controls and ethanol-treated animals, but after subsequent daily injections of amphetamine and cocaine, at doses that were insufficient to cause sensitization in controls, sensitization to both of these drugs was seen in ethanol-treated mice. When testing was started on the sixth day after cessation of the ethanol treatment, the effects of amphetamine on the first administration were significantly greater in ethanol-treated animals than in controls. After subsequent repeated daily injections, the locomotor stimulant effects of cocaine were greater in ethanol-treated mice than in controls. Administration of amphetamine for the first time 2 months after cessation of ethanol treatment also had a greater stimulant effect, compared with that in control animals. Two months after cessation of ethanol treatment, the first dose of cocaine caused a locomotor stimulation that was not seen in control animals, but sensitization was not seen after repeated cocaine administration in either group of animals. No differences in the effects of amphetamine or cocaine were seen after only 7 days of ethanol treatment. The results indicate that changes are still present in the CNS long after ethanol withdrawal hyperexcitability has subsided and that these changes result in increases in the effects of amphetamine and cocaine. Analysis of brain concentrations of the two psychostimulants suggested that metabolic changes were not responsible for the differing effects in control and ethanol-treated animals. It is possible that alterations in mesolimbic dopamine transmission are responsible for the effects of the ethanol treatment.