Dopamine and Isoproterenol Depolarize Corticotrophin Releasing Factor Neurons in the Bed Nucleus of the Stria Terminalis: A Potential Neurocircuit Involved in Relapse

Relapse is a significant challenge to successful treatment of addictions. Corticotrophin releasing factor (CRF) mediated activation of the bed nucleus of the stria terminalis (BNST) may play an important role in relapse behaviors. Previous reports suggest a serial circuitry in the BNST where drug‐associated cues, via increased dopamine levels, or exposure to stress, via increased norepinephrine levels, may increase CRF levels in the BNST thereby precipitating relapse. However, there is little evidence confirming this hypothetical neurocircuit. Thus, we sought to determine if dopamine or the β‐adrenergic receptor agonist, isoproterenol, can directly modify CRF neuron activity in the BNST. Mice expressing CRF fluorescent‐tagged neurons were used and CRF neuron activity was monitored using whole‐cell patch‐clamp electrophysiological methods. Acute application of dopamine and isoproterenol significantly depolarized BNST CRF neurons in persistent manner. Together with the finding that CRF enhances excitatory neurotransmission onto BNST projection neurons, these data suggest that both dopamine and isoproterenol may directly enhance CRF release from local BNST sources potentially precipitating relapse behaviors. Potential pharmacotherapies targeting this BNST circuit may be useful in the prevention of relapse to drug and alcohol addiction. Funding: NIH grants AA020140 and AA019455