Altered Fos expression in neural pathways underlying cue-elicited drug seeking in the rat

Cocaine treatment paired with environmental cues establishes a conditioned place preference for that environment. Following expression of this preference, rats show elevated levels of immediate early genes (e.g. c-fos) in the prelimbic cortex (PrL), basolateral amygdala complex (BLC) and nucleus accumbens core (NAcc) compared to drug-unpaired controls. The PrL and BLC are reciprocally connected and both project to the NAcc. Together with the immediate early gene findings, these connections suggest the regions interact as a circuit contributing to cue-elicited drug seeking. To study this circuit, we iontophoresed Fluorogold (FG) into one brain region and assessed colocalization of FG with place preference-induced Fos in the others. Following FG iontophoresis in either the PrL or NAcc, more BLC cells double-labelled for Fos and FG were found in drug-paired than unpaired animals. Following FG iontophoresis in either the BLC or NAcc, no differences were found in the absolute number of PrL Fos/FG cells. This pattern of colocalization suggests that exposure to cocaine-associated cues leads to greater activation of the BLC's efferents to both the PrL and NAcc, while PrL output to the NAcc and BLC is unaffected in IEG expression. These results complement recent findings that suggested attenuated PrL output during place preference expression. Our findings support the view that the BLC, rather than the PrL, provides significant excitatory driving to the NAcc during cue-elicited drug seeking.