6-Hydroxydopamine lesion of the dopamine mesocorticolimbic cell bodies increases (+)-amphetamine self-administration

The effect of 6-OHDA lesions of the dopaminergic mesocorticolimbic cell bodies on intravenous (+)-amphetamine self-administration in the rat was assessed. An acquisition paradigm was used in which the rat had to discriminate between an active and an inactive lever. Each press on the active lever delivered 7.5 g/kg (+)-amphetamine. The lesioned animals acquired this discrimination faster and hence self-administered a larger amount of drug. Thus dysfunction of dopaminergic neurons can induce an enhanced vulnerability to drugs which may be abused by humans.