State-dependent action of cocaine on brain temperature and movement activity: implications for movement sensitization.

ABSTRACT

Because neural activity is highly energy consuming and heat producing, brain temperature offers a reliable, real-time measure of an animal's activity state and its changes induced by environmental and drug challenges. Therefore, it allows evaluation of the activity state of an animal preceding drug administration and its relation to subsequent drug-induced neural effects. This approach was used to explore the state dependency of cocaine's effects. Brain and body temperatures, as well as locomotion were measured simultaneously in rats during repeated, daily administration of cocaine (15 mg/kg i.p., daily for 5 days) under different experimental conditions. The drug was administered via (a). a chronically implanted catheter in quiet resting conditions, (b). an injection made under quiet rest or (c). an injection under activated conditions associated with placement in the cage. Although brain temperature and movement increased after cocaine administration in each condition, cocaine's action (evaluated as cocaine-saline difference for both parameters) was situational. Catheter-administered cocaine induced the strongest movement activation and robust, monophasic temperature increase, which remained relatively stable following each subsequent drug infusion. Cocaine injected during quiet and, especially, activated conditions, induced a weaker locomotor activation, while the temperature response (evaluated as drug-saline difference) had a biphasic pattern. Cocaine initially inhibited the temperature increases seen in saline-treated animals (0-20 min) and then induced a more prolonged hyperthermia, which was about twofold weaker than that seen after catheter-administered drug. Although movement activation gradually increased following repeated treatment in activated conditions, the magnitude of this sensitized motor response barely reached the levels induced by the initial cocaine administration via catheter. These data suggest that both the acute effects of cocaine in the brain and their change following repeated drug administration are dependent upon the ongoing neural activity state of the animal. Cocaine's interaction with this activity state is a crucial factor determining the behavioral effects of this drug, including state-dependent motor sensitization.