The effect of long-term amphetamine administration on the activity of dopaminergic neurons of the substantia nigra.

Spontaneously active neurons from the pars compacta region of the substantia nigra were studied in chloral hydrate anesthetized, immobilized rats which had been pretreated with daily intraperitoneal saline or D-amphetamine injections according to several schedules. The spontaneous firing rates of these neurons were not altered by any of the pretreatment regimens. In addition, the intravenous dose of D-amphetamine sulfate which was required to reduce the spontaneous firing rate of these cells by at least 50% (threshold dose) was not modified by amphetamine pretreatment. There was a significant positive linear correlation between the threshold dose and the initial spontaneous firing rate of the neurons from animals pretreated with multiple saline injections, but not from those receiving long-term D-amphetamine. These results demonstrate that there are no alterations in the sensitivity of dopaminergic neurons to amphetamine under conditions known to produce the enhanced effects of the drug on motor behaviors which develop during multiple injections.