Maintenance of amphetamine-induced stereotypy and locomotion requires ongoing dopamine receptor activation

Abstract

Amphetamine-induced locomotion and stereotypy depend on dopamine (DA), yet, while extracellular DA concentrations peak early, and then begin to decline, intense stereotyped behaviors continue for relatively prolonged periods. These observations suggest that DA may act as a "trigger" for the entire multiphasic behavioral response. To test this hypothesis in rats, haloperidol (HAL) was injected at different times with respect to (AMPH), and automated and videotaped measures of the behavior were recorded. HAL (0.1 mg/kg, i.p.) or saline was administered either 15 min prior to AMPH (4.0 mg/kg, s.c.); 60 min following AMPH (during the phase of intense oral stereotypy); or 140 min after AMPH (during post-stereotypy locomotion). When administered prior to AMPH, HAL prevented the development of stereotypy, and an increase in locomotion was displayed in place of stereotypy. Haloperidol administration during stereotypy interrupted the response, and resulted in an increase in locomotion for the remainder of the stereotypy phase. In neither of these cases did HAL affect post-stereotypy locomotion. However, when injected during the post-stereotypy phase, HAL caused a decrease in the magnitude of the locomotor response, suggesting that both the stereotypy and locomotor components of the response remain sensitive to HAL at times when DA levels have significantly declined. These results do not support the hypothesis that the early increase in extracellular DA produced by AMPH, acts as a "trigger" for a non-dopaminergic receptor mediated expression of the later phases of the AMPH response. Instead, it appears that both stereotypy and post-stereotypy locomotion remain sensitive to DA receptor blockade when extracellular DA levels are below the levels produced by non-stereotypy-inducing doses of AMPH.