IBOTENIC ACID LESIONS OF THE DORSAL PREFRONTAL CORTEX DISRUPT THE EXPRESSION OF BEHAVIORAL SENSITIZATION TO COCAINE

Th present study determined the effect of bilateral lesions of specifi c cortical or thalamic nuclei that provide excitatory amino acid affer ents to the nucleus accumbens (i.e. the dorsal prefrontal cortex, vent ral prefrontal cortex, amygdala, hippocampus and periventricular thala mus) on the expression of cocaine-induced behavioral sensitization. Le sions of these nuclei were made during a three-week withdrawal period following repeated daily injections of cocaine or saline. The results indicate that dorsal prefrontal cortex lesions block the expression of behavioral sensitization to cocaine, while ventral prefrontal cortex, fimbria-fornix, amygdala and thalamic lesions have no effect. A subse quent microdialysis experiment was performed in order to evaluate the effect of dorsal prefrontal cortex lesions on glutamate transmission i n the nucleus accumbens core of cocaine-and saline-pretreated rats. Th e systemic injection of cocaine produced a significant increase in ext racellular glutamate in the nucleus accumbens core among animals with a sham surgery; this effect was blocked by a bilateral lesion of the d orsal prefrontal cortex. Taken together, these results indicate that t he dorsal prefrontal cortex, which provides excitatory amino acid inpu t selectively to the core region of the nucleus accumbens, enhances th e expression of behavioral sensitization to cocaine by increasing glut amate transmission in this subnucleus. (C) 1997 IBRO. Published by Els evier Science Ltd.