Abstract
We studied the involvement of cocaine- and amphetamine-regulated transcript peptide (CART) in the central nucleus of amygdala (CeA), lateral bed nucleus of the stria terminalis (BNSTl) and nucleus accumbens shell (AcbSh) in generation of ethanol withdrawal symptoms, with particular focus on anxiety-like behavior using a social interaction test. Administration of CART (54–102) into the lateral ventricle (50 and 100 ng) and bilaterally in the CeA (10 and 20 ng) caused a significant reduction in social interaction, suggesting an anxiogenic action of the peptide. Chronic ethanol treatment for 15 days followed by withdrawal precipitated an anxiogenic response at 24 h that was attenuated by intracerebroventricular (5 μl) and intra-CeA (1 μl) administration of antibodies against CART (1 : 500 dilution). An immunocytochemistry protocol was employed to study the response of the endogenous CART system in the CeA following chronic ethanol withdrawal. At 0 h ethanol withdrawal, CART immunoreactivity was apparent in few fibers and the profile was similar to that in the pair-fed control rats. Twenty-four hours following ethanol withdrawal, a highly significant increase (P<0.001) in CART immunoreactivity was noticed in the CeA, which returned to normal 48 and 72 h post-withdrawal. Similar doses of CART or CART antibody injected bilaterally into the BNSTl or AcbSh produced no response in the social interaction test. Furthermore, the CART immunoreactivity profile did not change at the post-withdrawal time points in each of these brain sites. We suggest that CART may mediate the early signs of anxiety-like behavior induced by ethanol withdrawal within the neuroanatomical framework of the CeA.
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Supported by the Grant from the Department of Science and Technology (SP/SO/C-39/99), Govt of India, New Delhi, India.
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The author(s) (MPD, PSS, DMK, RML, JJC, NS) declare that, except for income received from their primary employer, no financial support or compensation has been received from any individual or corporate entity over the past three years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. The author, LT is employed by and has equity interest with Novo Nordisk A/S, Denmark.
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Dandekar, M., Singru, P., Kokare, D. et al. Importance of Cocaine- and Amphetamine-Regulated Transcript Peptide in the Central Nucleus of Amygdala in Anxiogenic Responses Induced by Ethanol Withdrawal. Neuropsychopharmacol 33, 1127–1136 (2008). https://doi.org/10.1038/sj.npp.1301516
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DOI: https://doi.org/10.1038/sj.npp.1301516
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