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Single-unit activity was recorded in the substantia nigra pars reticulata of rats in response to intravenous challenge injections of D-amphetamine. The animals were pretreated with saline or 5.0 mg/kg D-amphetamine twice daily for 6 consecutive days. Whereas the large majority of saline controls (6 of 8) showed no consistent responses to amphetamine at doses up to 2.0 mg/kg, amphetamine pretreated rats (7 of 10) responded with a progressive increase in firing rate. Both groups of animals responded to a subsequent injection of 5.0 mg/kg clozapine with a depression of firing rate. The remaining control rats were inhibited by amphetamine and this aberrant response was enhanced with long-term treatment. In these unusual cells, clozapine accelerated firing rate. Taken together, these results indicate that unlike dopaminergic neurons in the compacta region of the nigra, reticulata neurons increase their responsiveness to amphetamine with repeated administration.
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