Asymmetric cross-sensitization to the locomotor stimulant effects of phencyclidine and MK-801

Abstract

Chronic administration of a psychomotor stimulant has been shown to produce progressively enhanced effects, a phenomenon called "reverse tolerance" or sensitization. Sensitization which develops to the psychomotor stimulant effect of a drug generalizes to drugs with similar neurochemical mechanisms of action, a phenomenon called cross-sensitization. The present study compared the psychomotor stimulant effects of phencyclidine and MK-801, examined the effects of the daily injection of phencyclidine and MK-801 on locomotor activity and investigated whether reciprocal cross-sensitization occurred between phencyclidine and MK-801. Adult female Sprague-Dawley rats were used. Their locomotor activity was measured automatically for a 2 h period following drug injection. Phencyclidine and MK-801 both increased locomotor activity. Four daily injections of phencyclidine in a dose of 3.2 mg/kg i.p., or MK-801 in a dose of 0.32 mg/kg i.p., produced sensitization to locomotor activity. Moreover, MK-801 sensitized rats showed cross-sensitization to phencyclidine. However, phencyclidine sensitized rats did not show cross-sensitization to MK-801. This finding suggests that there are significant differences in the neurochemical mechanisms underlying phencyclidine-induced and MK-801-induced sensitization. Phencyclidine sensitization may not be mediated by NMDA receptors.