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A blocker of n- and t-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement

Newton, Philip M., Zeng, Lily, Wang, Victoria, Connolly, Jacklyn, Wallace, Melisa Joellan, Kim, Chanki, Shin, Hee-Sup, Belardetti, Francesco, Snutch, Terrance P. and Messing, Robert O. 2008. A blocker of n- and t-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement. Journal of Neuroscience 28 (45) , pp. 11712-11719. 10.1523/JNEUROSCI.3621-08.2008

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Abstract

There is a clear need for new therapeutics to treat alcoholism. Here, we test our hypothesis that selective inhibitors of neuronal calcium channels will reduce ethanol consumption and intoxication, based on our previous studies using knock-out mice and cell culture systems. We demonstrate that pretreatment with the novel mixed N-type and T-type calcium channel antagonist 1-(6,6-bis(4-fluorophenyl)hexyl)-4-(3,4,5-trimethoxybenzyl)piperazine (NP078585) reduced ethanol intoxication. NP078585 also attenuated the reinforcing and rewarding properties of ethanol, measured by operant self-administration and the expression of an ethanol conditioned place preference, and abolished stress-induced reinstatement of ethanol seeking. NP078585 did not affect alcohol responses in mice lacking N-type calcium channels. These results suggest that selective calcium channel inhibitors may be useful in reducing acute ethanol intoxication and alcohol consumption by human alcoholics.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: alcoholism; calcium channel; N type; T type; contoxin; addiction; relapse
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 27/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 May 2016 02:16
URI: http://orca-mwe.cf.ac.uk/id/eprint/28864

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