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Publication : A blocker of N- and T-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement.

First Author  Newton PM Year  2008
Journal  J Neurosci Volume  28
Issue  45 Pages  11712-9
PubMed ID  18987207 Mgi Jnum  J:143196
Mgi Id  MGI:3823157 Doi  10.1523/JNEUROSCI.3621-08.2008
Citation  Newton PM, et al. (2008) A blocker of N- and T-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement. J Neurosci 28(45):11712-9
abstractText  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.
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