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Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A receptor-independent mechanism

Zanos, P, Wright, SR, Georgiou, P, Yoo, JH, Hourani, SM, Kitchen, I, Winsky-Sommerer, R, Bailey, A and Ledent, C (2014) Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A receptor-independent mechanism Pharmacology Biochemistry and Behavior, 119. pp. 72-79.

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Abstract

There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4 ml/kg/day, i.p.) or methamphetamine (1 mg/kg/day, i.p.) was administered daily for 10 days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A receptors which were chronically treated with methamphetamine (1 mg/kg/day, i.p. for 10 days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor system in brain regions associated with stress, emotionality and social bonding and that these neuroadaptations are independent on the presence of A receptors. These results may at least partly explain some of the behavioural consequences of chronic methamphetamine use. © 2013 Elsevier Inc. All rights reserved.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Zanos, PUNSPECIFIEDUNSPECIFIED
Wright, SRUNSPECIFIEDUNSPECIFIED
Georgiou, PUNSPECIFIEDUNSPECIFIED
Yoo, JHUNSPECIFIEDUNSPECIFIED
Hourani, SMUNSPECIFIEDUNSPECIFIED
Kitchen, IUNSPECIFIEDUNSPECIFIED
Winsky-Sommerer, RUNSPECIFIEDUNSPECIFIED
Bailey, AUNSPECIFIEDUNSPECIFIED
Ledent, CUNSPECIFIEDUNSPECIFIED
Date : April 2014
Identification Number : 10.1016/j.pbb.2013.05.009
Additional Information : NOTICE: this is the author’s version of a work that was accepted for publication in Pharmacology Biochemistry and Behavior. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacology Biochemistry and Behavior, 119, April 2014, DOI 10.1016/j.pbb.2013.05.009.
Depositing User : Symplectic Elements
Date Deposited : 04 Nov 2014 10:11
Last Modified : 08 Nov 2014 14:33
URI: http://epubs.surrey.ac.uk/id/eprint/806340

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