β-Adrenergic receptors enhance excitatory transmission in the bed nucleus of the stria terminalis through a corticotrophin-releasing factor receptor-dependent and cocaine-regulated mechanism

Abstract

Background: Evidence suggests that the noradrenergic and corticotrophin-releasing factor (CRF) systems play critical roles in relapse and stress-related behaviors. In particular, behavioral studies point to a serial signaling process initiated by β-adrenergic receptors that requires CRF receptor (CRFR)-dependent signaling in the bed nucleus of the stria terminalis (BNST) to produce stress-induced relapse to cocaine seeking.

Methods: We used whole cell patch clamp recordings from acutely prepared mouse brain slices to examine the actions of β-adrenergic receptors and CRFR1 on excitatory transmission in BNST. We examined the effects of agonists of these receptors in slices prepared from naive, sham, and cocaine-conditioned mice.

Results: β(1)-adrenergic receptor activation within the BNST produces an enhancement of excitatory synaptic transmission that requires CRFR1-dependent signaling. We show that chronic cocaine administration transiently disrupts β(1)-adrenergic- and CRFR1-dependent enhancement of glutamatergic transmission, that this disruption wanes with time, and that it can be reintroduced with a cocaine challenge.

Conclusions: In total, these studies identify a circuit mechanism within the BNST that may play an important role in CRF- and norepinephrine-regulated behaviors.