ENHANCEMENT OF AMPHETAMINE-INDUCED AND COCAINE-INDUCED LOCOMOTOR-ACTIVITY AFTER CHRONIC ETHANOL ADMINISTRATION

The effects of amphetamine and cocaine on locomotor activity in mice w ere studied after 3 weeks of chronic administration of ethanol by liqu id diet. When testing was started 24 h after cessation of the ethanol treatment, no differences were seen on the first administration betwee n the effects of the psychostimulants in controls and ethanol-treated animals, but after subsequent, daily injections of amphetamine and coc aine, at doses that were insufficient to cause sensitization in contro ls, sensitization to both of these drugs was seen in ethanol-treated m ice. When testing was started on the sixth day after cessation of the ethanol treatment, the effects of amphetamine on the first administrat ion were significantly greater in ethanol-treated animals than in cont rols. After subsequent repeated daily injections, the locomotor stimul ant effects of cocaine were greater in ethanol-treated mice than in co ntrols. Administration of amphetamine for the first time 2 months afte r cessation of ethanol treatment also had a greater stimulant effect, compared with that in control animals, Two months after cessation of e thanol treatment, the first dose of cocaine caused a locomotor stimula tion that was not seen in control animals, but sensitization was not s een after repeated cocaine administration in either group of animals. No differences in the effects of amphetamine or cocaine were seen afte r only 7 days of ethanol treatment, The results indicate that changes are still present in the CNS long after ethanol withdrawal hyperexcita bility has subsided and that these changes result in increases in the effects of amphetamine and cocaine. Analysis of brain concentrations o f the two psychostimulants suggested that metabolic changes were not r esponsible for the differing effects in control and ethanol-treated an imals. It is possible that alterations in mesolimbic dopamine transmis sion are responsible for the effects of the ethanol treatment.