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Alterations in ethanol‐induced accumbal transmission after acute and long‐term zinc depletion
Author(s) -
Morud Julia,
Adermark Louise,
Ericson Mia,
Söderpalm Bo
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.12096
Subject(s) - nucleus accumbens , microdialysis , chemistry , tricine , nmda receptor , ethanol , medicine , dopamine , gabaa receptor , excitatory postsynaptic potential , endocrinology , extracellular , biophysics , zinc , glutamate receptor , receptor , pharmacology , biochemistry , biology , organic chemistry
Alcoholism is subject to extensive research, but the role of changes in metabolism caused by alcohol consumption has been poorly investigated. Zinc ( Zn 2+ ) deficiency is a common metabolic aberration among alcoholics and Zn 2+ influences the function of ligand‐gated ion channels, known pharmacological targets of ethanol ( E t OH ). Here, we investigate whether manipulation of extracellular levels of Zn 2+ modulates E t OH ‐induced increases of dopamine ( DA ) output, as measured by in vivo microdialysis in the rat, and whether voluntary E t OH consumption is altered by Zn 2+ deficiency. Our findings show that the Zn 2+ ‐chelating agent tricine slowly raises DA levels when perfused in the nucleus accumbens (n A c), whereas the more potent Zn 2+ chelator TPEN reduces DA levels. We also show that pre‐treatment with either tricine or TPEN blocks the E t OH ‐induced DA elevation. Chronic Zn 2+ deficiency induced by a Zn 2+ ‐free diet did not affect E t OH consumption, but excitatory transmission, assessed by striatal field‐potential recordings in the n A c shell, was significantly modulated both by Zn 2+ ‐free diet and by E t OH consumption, as compared with the E t OH naïve controls. The present study indicates that Zn 2+ influences E t OH 's interaction with the brain reward system, possibly by interfering with glycine receptor and GABA A receptor function. This also implies that Zn 2+ deficiency among alcoholics may be important to correct in order to normalize important aspects of brain function.