Dopaminergic afferents from midbrain to dorsolateral bed nucleus of stria terminalis inhibit release and expression of corticotropin‐releasing hormone in paraventricular nucleus

Abstract Dopaminergic (DAergic) neurons of the midbrain ventral tegmental area (VTA) are known to regulate the hypothalamic‐pituitary‐adrenal (HPA) axis but have no direct projections to the paraventricular nucleus (PVN) of the hypothalamus. This study investigated whether VTA DAergic afferents modulate glutamatergic transmission‐dependent GABAergic neurons in dorsolateral bed nucleus of stria terminalis (dlBNST) to affect the activity of the HPA‐axis. Herein, we demonstrate that systemic administration of the neurotoxicant 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) or the VTA‐injection of 1‐methyl‐4‐phenylpyridinium ion (MPP+) in male mice (MPTP‐mice and MPP+mice) caused a decline of tyrosine hydroxylase positive (TH+) cells in VTA with a reduction in TH+fibers in the dlBNST. MPTP‐mice and MPP+mice displayed a clear increase in serum levels of corticosterone (CORT) and adrenocorticotropic hormone, corticotropin‐releasing hormone (CRH) expression, and CRH neuron activity in PVN. The presynaptic glutamate release, glutamatergic synaptic transmission and induction of long‐term potentiation in dlBNST of MPTP‐mice were suppressed, and these effects were rescued by a D1‐like DAergic receptor (D1R) agonist and mimicked in control dlBNST by blockade of D1R. MPTP‐mice exhibited low expression of glutamic acid decarboxylase and dysfunction of the excitatory‐dependent GABAergic circuit in dlBNST, and these effects were recovered by the administration of D1R agonist. Furthermore, either dlBNST‐injection of D1R agonist or PVN‐injection of GABA A receptor (GABA A R) agonist could correct the increased secretion and expression of CRH in MPTP‐mice. The results indicate that the DAergic afferents from VTA enhance excitatory‐dependent activation of GABAergic neurons in dlBNST, which suppress the activity of the HPA‐axis. image