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The N-type calcium channel is a novel target for treating alcohol use disorders

Philip M. Newton and Robert O. Messing

We recently validated the N-type calcium channel as a target for the treatment of alcoholism and anxiety. N-type calcium channels are neuronal presynaptic ion channels that regulate neurotransmitter release at many sites in the brain. Mice lacking N-type calcium channels exhibit reduced ethanol consumption and show resistance to the acute intoxicating effects of ethanol. In wild type rodents, pretreatment with a novel N- and T-type calcium channel blocker, NP078585, reduces the intoxicating and reinforcing effects of ethanol and abolishes stress-induced reinstatement of alcohol seeking. Here we discuss these findings and expand upon their implications for the N-type calcium channel as a target for drug development. An important consideration in the development of drugs to treat any addiction is that the medication itself not be addictive. We attempted, and failed, to generate a conditioned place preference for NP078585, suggesting that NP078585 is not rewarding.

Newton PM, Zeng L, Wang V, Connolly J, Wallace MJ, Kim C, Shin HS, Belardetti F, Snutch TP, Messing RO.A blocker of N- and T-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement. J Neurosci. 2008 Nov 5;28(45):11712-9.

Authors

Philip M. Newton

Ernest Gallo Clinic and Research Center, UCSF

Robert O. Messing Corresponding author: romes@gallo.ucsf.edu

Ernest Gallo Clinic and Research Center, UCSF