Fos protein expression and cocaine-seeking behavior in rats after exposureto a cocaine self-administration environment

To examine neuronal activation associated with incentive motivation for coc aine, cocaine-seeking behavior (operant responding without cocaine reinforc ement) and Fos expression were examined in rats exposed to saline and cocai ne priming injections and/or a self-administration environment. Rats were f irst trained to self-administer cocaine or received yoked saline administra tion ("control"). They then received 21 daily exposures to either the self- administration environment ("extinction") or a different environment ("no e xtinction") without cocaine available. Extinction training, used to decreas e incentive motivation for cocaine elicited by the self-administration envi ronment, decreased cocaine-seeking behavior elicited by both the environmen t and the cocaine priming injection. Exposure to the self-administration en vironment enhanced Fos expression in the no extinction group relative to co ntrol and extinction groups in the anterior cingulate, basolateral amygdala , hippocampal CA1 region, dentate gyrus, nucleus accumbens shell and core, and central gray area, regardless of whether or not priming injections were given. The priming injections enhanced Fos expression in the ventral tegme ntal area, caudate putamen, substantia nigra pars reticulata, entorhinal co rtex, central amygdala, lateral amygdala, arcuate nucleus, and central gray area, regardless of group. Thus, these changes likely reflect an unconditi oned effect from either cocaine or injection stress. The priming injections also enhanced Fos expression in the anterior cingulate, but only in cocain e-experienced groups, suggesting that this enhancement reflects an experien ce-dependent motivational effect of the priming injections. The results sug gest that different neural circuits may be involved in the incentive motiva tional effects of cocaine-paired environmental stimuli versus priming injec tions and that the anterior cingulate may be part of a common pathway for b oth.