Attempts were made to elucidate the neurochemical mechanisms underlying behavioral sensitization induced by chronic administration of amphetamine. Rats were treated daily for seven days with 3 mg/kg of amphetamine and then challenged on day eight or eleven with a lower dose of this stimulant. Microdialysis studies, as well as behavioral analyses, were conducted on the challenge days. Amphetamine applied to the terminal fields of the dopamine pathways elicited a dose-dependent increase in dopamine overflow. No differences were found between animals tested chronically with amphetamine or saline tested either one or four days following termination of treatment. A systemic challenge (subcutaneous) at 1.0 mg/kg also did not reveal a difference in the dopamine response between the two groups. A challenge with 0.25 mg/kg, however, one day following termination of treatment, did reveal a more prolonged increase in striatal dopamine overflow in the chronic amphetamine group, although the peak effect was no different from the controls. Behavioral sensitization was seen in both stereotypy and locomotor activity with the drug regimen used in these studies. While it is possible that increased responsivity of the dopamine system to amphetamine may underlie some aspects of behavioral sensitization, pharmacokinetic factors must also be considered.
