Clozapine and haloperidol in the amygdaloid complex: differential effects on dopamine transmission with long-term treatment.

Single-unit recording techniques and liquid chromatography with electrochemical detection were used to measure the effects of neuroleptic pretreatment on the efficacy of dopamine transmission in the amygdaloid complex. Rats received twice-daily injections of clozapine (10.0 mg/kg), haloperidol (1.0 mg/kg), or vehicle for 6 days. During withdrawal from haloperidol, but not clozapine, amygdaloid neurons were significantly more responsive to iontophoretic application of dopamine. Neither drug altered the neuronal response to norepinephrine or acetylcholine. Tolerance developed to the ability of haloperidol to increase the amygdaloid level of 3,4-dihydroxyphenylacetic acid (DOPAC), a major dopamine metabolite, but such an effect did not occur with clozapine. In fact, clozapine pretreatment led to a significant increase in both DOPAC and dopamine levels in the amygdaloid complex. These results suggest that a differential action of these drugs on dopamine transmission may explain their differential effects on postsynaptic dopamine receptors.