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TitleA Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats
Author(s)Normandeau, Catherine P.
Silva, Ana Paula Ventura
Hawken, Emily R.
Angelis, Staci
Sjaarda, Calvin
Liu, Xudong
Pêgo, José M.
Dumont, É. C.
Behavior, Animal
Chronic Disease
Corticotropin-Releasing Hormone
Disease Models, Animal
Neural Inhibition
Rats, Long-Evans
Rats, Wistar
Receptors, Neurotensin
Synaptic Transmission
Septal Nuclei
Stress, Psychological
Issue dateJan-2018
PublisherSpringer Nature
CitationNormandeau, C. P., Ventura-Silva, A. P., Hawken, E. R., Angelis, S., et. al.(2018). A key role for neurotensin in chronic-stress-induced anxiety-like behavior in rats. Neuropsychopharmacology, 43(2), 285
Abstract(s)Chronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.
DescriptionAccepted Manuscript
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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