Time-dependent changes in the sensitivity of dopamine neurons to low doses of apomorphine following amphetamine infusion.

Changes in dopamine autoregulatory mechanisms following a chronic infusion of amphetamine were studied. Rats were infused with D-amphetamine (4.8 mg/day) for 7 days by osmotic minipumps, and were studied at various times after withdrawal. In contrast to no changes in the spontaneous firing rate of single dopamine cells, the potency of apomorphine in the substantia nigra was markedly decreased soon after withdrawal, followed by an increase 7 days later. The ventral tegmental area showed no changes in either spontaneous firing rate or sensitivity to apomorphine following a 7-day withdrawal. Moderate decreases in striatal and tubercle dopamine concentrations were not accompanied by any significant decrease in basal dopamine synthesis. Under intact impulse-flow, the sensitivity of terminal dopamine synthesis to low doses of apomorphine was decreased immediately following withdrawal; by Day 7 supersensitivity was observed. Direct assessment of terminal autoreceptors following a 7-day withdrawal revealed normo- and supersensitivity of these receptors in the striatum and olfactory tubercle, respectively. Possible mediating mechanisms as well as implications of these findings for the development of characteristic behavioral syndromes during and after amphetamine infusion are discussed.