Sensitization of amphetamine-induced stereotyped behaviors during the acute response

The quantitative and qualitative features of the behavioral response to amphetamine-like stimulants in rats can be dissociated from the dopamine response. This dissociation is particularly evident in the temporal profiles of the extracellular dopamine and stereotypy responses to higher doses of amphetamine. One possible mechanism contributing to this temporal dissociation is that during the acute response to amphetamine, dopamine receptor mechanisms are enhanced such that stereotyped behaviors can be supported by synaptic concentrations of dopamine which are not sufficient to initiate these behaviors. To further explore the dynamics of stimulant sensitivity during the acute response, we examined the behavioral and extracellular dopamine responses to a low, nonstereotypy-producing dose of amphetamine (0.5 mg/kg) at various times after an acute, priming injection of 4.0 mg/kg when stereotypies had subsided and extracellular dopamine was approaching predrug baseline levels. The low-dose challenge produced intense stereotypies although the regional dopamine responses were not significantly different from control animals. Blockade of the expression of stereotypies during the priming response by the D2 antagonist haloperidol or the D1 antagonist SCH 23390 prevented the expression of an enhanced stereotypy response to the challenge injection. Our results suggest that an exposure to amphetamine results in a rapid sensitization of the stereotypy response which does not involve changes in the extracellular dopamine response but requires activation of dopamine receptors. Such a mechanism may be significantly implicated during binge patterns of stimulant abuse and may also play a role in the sensitization associated with repeated amphetamine administration.