Neurokinin-1 receptor antagonists block acute cocaine-induced horizontal locomotion.

Systemic exposure to neurokinin-1 receptor antagonists CP099994 or LY306740 prior to cocaine administration (10 mg/kg i.p.) blocks acute, cocaine-induced horizontal locomotion. CP099994 (30 mg/kg) was delivered i.p. 30 minutes before cocaine exposure, and LY306740 (5 mg/kg) was delivered continuously by osmotic minipump for 12-14 hours before cocaine administration. These results suggest that endogenous substance P acting via neurokinin-1 receptors is necessary for the expression of acute cocaine-induced hyperactivity.