Long-term d-amphetamine in rats: lack of change in post-synaptic dopamine receptor sensitivity

Treatment of rats with d-amphetamine (5 mg/kg) once daily for 25 days did not change locomotor responses, on day 7 of withdrawal, to dopamine (DA) or d-amphetamine into the nucleus accumbens. Nor was there a change in 3H-spiperone binding of caudate nucleus membranes. There was no effect of treatment on the locomotor response of rats to 1.0, 1.5 or 2.0 mg/kg d-amphetamine IP. However, d-amphetamine-treated rats were significantly less sensitive to 0.5 mg d-amphetamine. Although 1, 2 or 3 mg/kg apomorphine produced in same degree of stereotypy in both treatment groups, there was a significant difference in the response of the two groups to 0.5 mg apomorphine, d-amphetamine-treated animals being less sensitive than vehicle-treated animals. No change was found in brain DA levels with or without synthesis inhibition. The present data do not support the hypothesis that chronic treatment of rats with d-amphetamine can produce supersensitive post-synaptic DA receptors.