Increase in mesolimbic electrical self-stimulation after chronic haloperidol: reversal by L-DOPA or lithium

After chronic neuroleptic drug treatment, an increase in electrical intracranial self-stimulation (ICSS) rate is seen from electrodes in the A10 dopaminergic nucleus. This increase, which persists for approximately 3 weeks following drug withdrawal, is believed to represent a behavioral manifestation of drug-induced dopaminergic synaptic supersensitivity. Chronic L-DOPA caused a partial reversal of haloperidol-induced ICSS increase. Lithium carbonate, given concurrently with the haloperidol, partially prevented the development of ICSS supersensitivity. It is concluded that dopaminergic synaptic sensitivity has a two-way modulatory capability.