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Alpha‐melanocyte stimulating hormone modulates ethanol self‐administration in posterior ventral tegmental area through melanocortin‐4 receptors
Author(s) -
Shelkar Gajanan P.,
Kale Atmaram D.,
Singh Uday,
Singru Praful S.,
Subhedar Nishikant K.,
Kokare Dadasaheb M.
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12126
Subject(s) - ventral tegmental area , nucleus accumbens , melanocortin , endocrinology , medicine , tyrosine hydroxylase , self administration , chemistry , antagonist , stria terminalis , dopamine , receptor , hypothalamus , pharmacology , dopaminergic
Abstract Although the role of alpha‐melanocyte stimulating hormone (α‐ MSH ) in alcohol seeking behaviour in rats has been demonstrated, the underlying mechanisms are not understood. Herein, we test the hypothesis that α‐ MSH might have a permissive effect in promoting the reward action of ethanol. Rats were implanted with cannulae targeted at the posterior ventral tegmental area ( pVTA ), because the site is sensitive to reinforcing effects of ethanol. These rats were trained to self‐administer ethanol in standard two‐lever (active/inactive) operant chamber test. Each active lever press resulted in self‐administration of 100 nl of ethanol (100–300 mg%) containing solution. Over a period of 7 days, ethanol significantly increased the number of lever presses, which was considered as a measure of reward. Because ethanol at 200 mg% resulted in maximum number of lever presses (∼18–20 lever presses/30‐minute session), the dose was employed in further studies. While prior administration of melanocortin ( MC ) agonists, α‐ MSH or [ N le4, D ‐ P he7]‐alpha‐ MSH into pVTA , resulted in an 89% increase in lever presses, the response was attenuated following pre‐treatment with MC 4 receptors ( MC 4 R ) antagonist, HS 014. In an immunohistochemical study, the brains of rats that were trained to self‐infuse ethanol showed significantly increased α‐ MSH immunoreactivity in the nucleus accumbens shell, bed nucleus of stria terminalis and arcuate nucleus of the hypothalamus. In the pVTA, α‐ MSH fibres were found to run close to the dopamine cells, labelled with tyrosine hydroxylase antibodies. We suggest that α‐ MSH ‐ MC 4 R system in the pVTA might be a part of the neuroadaptive mechanism underlying ethanol addiction.