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

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