Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat

Abstract

Cocaine is believed to exert its psychostimulant effects through activation of the mesocorticolimbic system. Although the nucleus accumbens, in particular, has been hypothesized as the site of action of cocaine's stimulating effects, there is no direct evidence that microinjection of cocaine into this region produces behavioral activation. The present experiments investigated the locomotor response to microinjection of cocaine (0, 10, 30, 100 μg/0.5 μl) into the nucleus accumbens in rats. Cocaine elicited a pronounced, dose-dependent motor activation of approximately 60 min duration. This stimulant effect was blocked by prior administration of a dopamine (DA) receptor antagonist, cis-flupenthixol. The response to cocaine was differentiated from nucleus accumbens microinjections of procaine and lidocaine, compounds that have potent local anesthetic effects but little affinity for the dopamine-uptake site. Neither procaine nor lidocaine (0, 10, 30, 100 μg/0.5 μl) had any overall effect, although activity was somewhat decreased in the initial part of the test session and increased at the end, relative to control activity. Cocaine injected into the anterior dorsal or ventrolateral striatum (100 μg) also increased motor activity; procaine and lidocaine had no effect. Cocaine injected into the ventrolateral striatum significantly increased stereotypy. The amplitude of motor activation following cocaine injection into nucleus accumbens was much greater than that elicited at the other striatal sites. Further, observation of the time course of motor activation following cocaine injection into the anterior dorsal and ventrolateral striatum suggested that the motor effect was due to diffusion, most likely to the nucleus accumbens. The results show that cocaine can be microinjected with a considerable degree of specificity, and they support the hypothesis that the nucleus accumbens is the major site of cocaine's stimulant action.