Abstract
Lewis rats show increased anxiety-like behaviors and drug consumption compared with Sprague-Dawley rats. Prior work suggests norepinephrine (NE) signaling in the bed nucleus of the stria terminalis (BNST) could have a role in mediating these phenotypes. Here, we investigated NE content and dynamics in the ventral BNST (vBNST) using fast-scan cyclic voltammetry in these two rat strains. We found that NE release evoked by electrical stimulus and its subsequent uptake was dysregulated in the more anxious Lewis rats. Because addiction is a multifaceted disease influenced by both genetic and environmental factors, we hypothesized NE dynamics would vary in these strains after the induction of a physical dependence on morphine. Following naloxone-precipitated morphine withdrawal, NE release and uptake dynamics were not changed in Lewis rats but were significantly altered in Sprague-Dawley rats. The alterations in Sprague-Dawley rats were accompanied by an increase in anxiety-like behavior in those animals as measured with the elevated plus maze. These studies suggest novel mechanisms involved in the development of affective disorders, and highlight the noradrenergic system in the vBNST as a common substrate for the manifestation of pathological anxiety and addiction.
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Acknowledgements
We thank Dr Michael Saddoris for advice on statistical methods, Dr Ryan Vetrano and Dr Fulton Crews for behavioral advice and assistance, and Elyse Dankoski and Dr Thomas Kash for comments on an earlier version of the manuscript. This work was supported by an NIH grant (NS15841) to RMW and the NIMH Psychoactive Drug Screening Program Contract to BLR.
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BLR has received research support from Dai-Nippon Sumitomo and has been a consultant to Pfizer Pharmaceuticals, SeaChange Pharmaceuticals, Finnegan, Henderson, Faraboug, Garnett and Henderson LLP and Dai-Nippon Sumitomo Pharmaceuticals. BLR also receives payment from the Journal of Clinical Investigation for his duties as Associate Editor of the JCI. The remaining authors declare no conflict of interest.
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McElligott, Z., Fox, M., Walsh, P. et al. Noradrenergic Synaptic Function in the Bed Nucleus of the Stria Terminalis Varies in Animal Models of Anxiety and Addiction. Neuropsychopharmacol 38, 1665–1673 (2013). https://doi.org/10.1038/npp.2013.63
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DOI: https://doi.org/10.1038/npp.2013.63
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