Yohimbine anxiogenesis in the elevated plus maze is disrupted by bilaterally disconnecting the bed nucleus of the stria terminalis from the central nucleus of the amygdala.
The α2 adrenergic receptor antagonist yohimbine (YO) is a sympathomimetic drug that crosses the blood-brain barrier after systemic administration. YO promotes increased transmitter release from noradrenergic (NA) axon terminals in the central nucleus of the amygdala (CEA), bed nucleus of the stria terminalis (BST), hypothalamus, and other brain regions implicated in physiological and behavioral responses to stressful and threatening stimuli. YO is potently anxiogenic in humans and experimental animals, including rats. To determine whether direct connections between the CEA and anterolateral group of BST nuclei (algBST) are necessary for YO anxiogenesis in rats, neurotoxic ibotenate lesions of the CEA in one hemisphere and the ipsi- or contralateral algBST were conducted to disrupt CEA-algBST communication uni- or bilaterally. Sham-lesioned controls received microinjections of vehicle into the CEA and algBST. Two weeks later, behavior was assessed in the elevated plus maze (EPMZ) in rats after i.p. saline or YO (1.0mg/kg). Central ibotenate lesion placement and extent was assessed post-mortem in NeuN-immunolabeled tissue sections. The ability of YO to increase anxiety-like behavior in the EPMZ was similarly robust in rats with sham lesions or ipsilateral CEA-algBST lesions. Conversely, YO anxiogenesis in the EPMZ was disrupted in rats with asymmetric lesions designed to bilaterally disconnect the CEA and algBST, whereas neither unilateral nor bilateral disconnecting lesions altered EPMZ behavior in rats after i.p. saline. We conclude that the anxiogenic effects of increased NA signaling in rats after YO require direct CEA-algBST interactions that do not shape EPMZ behavior under baseline conditions.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, United States.
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Bakalli
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Rinaman
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009434:Neural Pathways / Q000293:injuries / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D014741:Video Recording; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D015016:Yohimbine; D010751:Phosphopyruvate Hydratase