Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Nov 2018
The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway.
Previous preclinical and clinical investigations have focused on the L-type calcium channel (LTCC) as a potential therapeutic target for substance abuse. While some clinical studies have examined the ability of LTCC blockers to alter cocaine's subjective effects, very few LTCC studies have examined cocaine relapse. Here, we examined whether ventral tegmental area (VTA)-specific or systemic administration of the LTCC inhibitor, isradipine, altered cocaine-seeking behavior in a rat model. ⋯ Surprisingly in our study, isradipine enhanced tonic and phasic DA signaling in cocaine abstinent rats, with no change in sucrose abstinent nor naïve rats. Strikingly, isradipine's behavioral effects were dependent upon NAc core DA receptor activation. Together, our findings reveal a novel mechanism by which the FDA-approved drug, isradipine, could act to decrease cocaine relapse.