Dataset Information

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence.

ABSTRACT: It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons. We then measured alcohol self-administration and cue-induced reinstatement of alcohol seeking in dependent and nondependent rats after intracerebroventricular (i.c.v.) injection of the LTCC antagonist verapamil, as well as in mice with an inducible knockout (KO) of Cav1.2 in Ca2+/calmodulin-dependent protein kinase II? (CaMKII?)-expressing neurons. Our results show that Cacna1c mRNA concentration was increased in the amygdala and hippocampus of alcohol-dependent rats after 21 days of abstinence, with no changes in Cacna1d mRNA. This was associated with increased Cav1.2 protein concentration and L-type calcium current amplitudes. Further analysis of Cacna1c mRNA in the CA1, basolateral amygdala (BLA), and central amygdala (CeA) revealed a dynamic regulation over time during the development of alcohol dependence. The inhibition of central LTCCs via i.c.v. administration of verapamil prevented cue-induced reinstatement of alcohol seeking in alcohol-dependent rats. Further studies in conditional Cav1.2-KO mice showed a lack of dependence-induced increase of alcohol-seeking behavior. Together, our data indicate that central Cav1.2 channels, rather than Cav1.3, mediate alcohol-seeking behavior. This finding may be of interest for the development of new antirelapse medications.

SUBMITTER: Uhrig S

PROVIDER: S-EPMC5506795 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence.

Uhrig Stefanie S Vandael David D Marcantoni Andrea A Dedic Nina N Bilbao Ainhoa A Vogt Miriam A MA Hirth Natalie N Broccoli Laura L Bernardi Rick E RE Schönig Kai K Gass Peter P Bartsch Dusan D Spanagel Rainer R Deussing Jan M JM Sommer Wolfgang H WH Carbone Emilio E Hansson Anita C AC

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20161201 5

It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings ...[more]

PMID: 27905406

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Dataset Information

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence.

Publications

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence.

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