A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats

Rationale: We reported previously that bilateral injection of a corticotropin-releasing factor (CRF)receptor antagonist, D-Phe CRF12-41, into the bed nucleus of the stria terminalis (BNST) blocks the reinstatement of cocaine seeking induced by footshock, whereas the injection of CRF into the same region induces reinstatement. One source of CRF in the BNST arises from a CRF-containing projection originating in the central nucleus of the amygdala (CeA). Objective: To determine whether the CRF-containing projection from the amygdala to the BNST is involved in the mediation of stress-induced reinstatement of cocaine seeking by functionally interrupting the pathway. Methods: Rats trained to self-administer cocaine (1 mg/kg, IV, 9 days) were given extinction sessions after a 10- to 11-day drug-free period, followed by tests for stress-induced reinstatement (footshock: 15 min intermittent 0.8-mA footshocks given immediately before presentation of the previously active lever). Before the tests, animals were pretreated with either: (1) TTX (2.5 ng) in amygdala (including the CeA) in one hemisphere and D-Phe CRF12-41 (50 ng) in BNST in the other, (2) unilateral TTX, or (3) unilateral D-Phe. Results: Footshock reinstated cocaine seeking following unilateral injections of either TTX in amygdala or D-Phe in BNST, but following the injection of both TTX in amygdala and D-Phe in BNST the effects of footshock were greatly attenuated. Conclusion: These results suggest that the CRF-containing pathway from CeA to BNST is involved in mediating the effects of CRF and its receptor antagonist in the BNST on the reinstatement of cocaine seeking.