Noradrenaline triggers GABA_A inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area

The lateral part of the ventral bed nucleus of the stria terminalis (v1BNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the v1BNST after withdrawal from a 5 d treatment with morphine. The v1BNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated α₁-adrenergic receptors to increase-GABA_A-IPSC frequency. Noradrenaline produced a similar increase in GABA_A-IPSCs during acute opioid withdrawal, but this increase resulted from activation of β-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as α₁-adrenergic receptors. Given that neurons in the v1BNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal.