Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis.
The α2 adrenergic receptor antagonist yohimbine (YO) increases transmitter release from noradrenergic (NA) terminals in cortical and subcortical brain regions, including the bed nucleus of the stria terminalis (BST). YO activates the hypothalamic-pituitary-adrenal (HPA) stress axis and is potently anxiogenic in rats and humans. We previously reported that hindbrain NA neurons within the caudal nucleus of the solitary tract (NST-A2/C2) and ventrolateral medulla (VLM-A1/C1) that innervate the anterior ventrolateral (vl)BST contribute to the ability of YO to activate the HPA stress axis in rats. To determine whether the same NA pathway also contributes to YO-induced anxiogenesis in the elevated plus maze (EPMZ), a selective saporin ribotoxin conjugate (dopamine beta hydroxylase conjugated to saporin toxin, DSAP) was microinjected bilaterally into the anterior vlBST to destroy its NA inputs. Sham-lesioned controls were microinjected with vehicle. Two experiments were conducted to determine DSAP lesion effects on EPMZ behavior. DSAP lesions did not alter maze behavior in rats after intraperitoneal saline, and did not alter the significant effect of prior maze experience to reduce exploratory and open arm maze activities. However, in maze-naïve rats, DSAP lesions abolished YO anxiogenesis in the EPMZ. Post-mortem immunocytochemical analyses confirmed that DSAP consistently ablated caudal NST-A2/C2 and VLM-A1/C1 neurons that innervate the anterior vlBST. DSAP lesions did not destroy non-NA inputs to the anterior vlBST, and produced inconsistent cell loss within the pontine locus coeruleus (A6 cell group) that was unrelated to YO anxiogenesis. Thus, the ability of YO to increase anxiety-like behavior in the EPMZ depends on hindbrain NA neurons that target the anterior vlBST.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Huiyuan
H
Zheng
Linda
L
Rinaman
D059331:Adrenergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine