A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking

We have shown that intracerebroventricular administration of the corticotro pin-releasing factor (CRF) receptor antagonist D-Phe CRF12-41, blocks foots hock-induced reinstatement of drug seeking in cocaine-trained rats. We now report that D-Phe acts in the bed nucleus of the stria terminalis (BNST), a nd not in the amygdala, to block footshock-induced reinstatement of cocaine seeking. In addition, CRF injections in the BNST, and not in the amygdala, are sufficient to reinstate cocaine seeking. Rats were trained to self-adm inister cocaine intravenously on a fixed ratio (FR-1) schedule of reinforce ment. After 5 drug-free days, animals were returned to the self-administrat ion chambers and given daily extinction and reinstatement test sessions. To test the effects of D-Phe CRF12-41 on stress-induced reinstatement, rats w ere pretreated with vehicle or D-Phe in either the BNST (10 or 50 ng per si de) or amygdala (50 or 500 ng per side) before being exposed to 15 min of i ntermittent footshock stress. To test whether injections of CRF itself coul d induce reinstatement, rats were given vehicle or CRF in either the BNST ( 100 or 300 ng per side) or amygdala (300 ng per side) 15 min before the ses sion. Injections of D-Phe into the BNST completely blocked footshock-induce d reinstatement of cocaine seeking; injections of CRF itself in this struct ure induced reinstatement. Injections of these compounds into the amygdala were without effect. These findings suggest that activation of CRF receptor s in the BNST, but not in the amygdala, is critical for footshock-induced r einstatement of cocaine seeking.