Alterations in ethanol‐induced accumbal transmission after acute and long‐term zinc depletion. (16th September 2013)

• Record Type: Journal Article
• Authors: Morud, Julia; Adermark, Louise; Ericson, Mia; Söderpalm, Bo
• Is Part Of: Addiction biology. Volume 20:Number 1(2015:Jan.)
• Page Start: 170
• Page End: 181
• Publication Date: 2013-09-16
• Subjects: Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12096
• Languages: English
• ISSNs: 1355-6215

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Alcoholism is subject to extensive research, but the role of changes in metabolism caused by alcohol consumption has been poorly investigated. Zinc (Zn<sup>2+</sup>) deficiency is a common metabolic aberration among alcoholics and Zn<sup>2+</sup> influences the function of ligand‐gated ion channels, known pharmacological targets of ethanol (EtOH). Here, we investigate whether manipulation of extracellular levels of Zn<sup>2+</sup> modulates EtOH‐induced increases of dopamine (DA) output, as measured by <italic>in vivo</italic> microdialysis in the rat, and whether voluntary EtOH consumption is altered by Zn<sup>2+</sup> deficiency. Our findings show that the Zn<sup>2+</sup>‐chelating agent tricine slowly raises DA levels when perfused in the nucleus accumbens (nAc), whereas the more potent Zn<sup>2+</sup> chelator TPEN reduces DA levels. We also show that pre‐treatment with either tricine or TPEN blocks the EtOH‐induced DA elevation. Chronic Zn<sup>2+</sup> deficiency induced by a Zn<sup>2+</sup>‐free diet did not affect EtOH consumption, but excitatory transmission, assessed by striatal field‐potential recordings in the nAc shell, was significantly modulated both by Zn<sup>2+</sup>‐free diet and by EtOH consumption, as compared with the EtOH naïve controls. The present study indicates that Zn<sup>2+</sup> influences EtOH's interaction with the brain reward system, possibly by interfering with glycine receptor and GABA<sub>A</sub> receptor function. This also implies that Zn<sup>2+</sup> deficiency among alcoholics may be important to correct in order to normalize important aspects of brain function.</p> </abstract>