Oral cocaine self-administration: Relation of locomotor activity to pharmacokinetics

Abstract

Rats were exposed to daily schedule-induced polydipsia sessions in which solutions of cocaine HCl were available. Both cocaine solution concentration (0.08–0.32 mg/ml) and session duration (0.25–3 h) were varied to determine their effects on locomotor activity rate. Additional animals were used to determine the effect of session length on serum cocaine and metabolite levels when drinking 0.32 mg/ml cocaine solution. Changes in locomotor activity rate were related to serum cocaine concentration by a linear concentration-effect model. By estimation from the linear model, the serum cocaine concentration threshold for increasing locomotor activity was about 0.01 μg/ml. Under these schedule-induction conditions, there was no evidence for the development of acute tolerance to the locomotor-stimulating activity of cocaine.