Development and reversal of sensitization to amphetamine-induced hypophagia: role of temporal, pharmacological, and behavioral variables.

This study shows that sensitization can develop to amphetamine-induced hypophagia and examines the stability of this effect following subsequent pharmacological and behavioral experience. Rats given 36 injections of either amphetamine (2.5 mg/kg; Group A) or saline (Group S) at 3-day intervals developed sensitization of hypophagia, as assessed by a shift to the left in the dose-response (DR) function. Group A also displayed sensitization of stereotypy, whereas Group S showed little change except at the highest dose. Subgroups from each group were then given daily injections of amphetamine (2 mg/kg) either before or after access to milk for 4 weeks. Other subgroups were given injections of saline as a control. On a final DR determination, these control groups showed no further changes in milk intake. In contrast, groups given chronic injections of amphetamine after milk showed a loss of sensitization (DR3 = DR1), whereas groups given the drug before milk developed tolerance that was limited to the chronic dose. These results demonstrate that (1) sensitization of amphetamine-induced hypophagia and stereotypy can develop independently; (2) sensitization of hypophagia can be reversed, without inducing tolerance, by subsequent daily exposure to the drug; and (3) prior sensitization of hypophagia does not preclude the subsequent development of tolerance if the drug is later given in the context of feeding.