GABAergic supersensitivity within the pars reticulata of the rat substantia nigra following chronic haloperidol administration

These studies were performed to evaluate the effects of chronic haloperidol administration on the responsiveness of the pars reticulata neurons of the substantia nigra (SN R) to microiontophoretically applied γ-aminobutyric acid (GABA) and glycine. Rats were administered haloperidol in their feed (CHAL treatment) for 30 days in increasing concentrations. All experiments were conducted two days after termination of the CHAL treatment. GABA receptor binding and neuronal responsiveness to GABA were significantly increased within the SN R following CHAL treatment. The mean EC 50 value for GABA was significanly decreased for SN R neurons in CHAL-treated rats, but there was no change in the EC 50 for glycine. Specific [ 3H]GABA binding (4nM) was elevated by more than 50% within the SN R. Scatchard analysis of [ 3H]muscimol binding data revealed that the binding capacities ( B max) of both high and low affinity GABA binding sites within the SN R were significantly increased without a change in the apparent dissociation constants ( K d) of either site. Although no regional difference in responsiveness to GABA was detected within the SN R of CHAL-treated rats, the spontaneous activity of neurons located within the rostral two-thirds of the nucleus was reduced; however, there was no change in spontaneous activity of neurons located within the caudal one-third. These data provide direct physiological evidence to support the conclusion that the increase in GABA binding within the SN R following CHAL treatment reflects a neuronal supersensitivity to GABA.