Mechanisms of Disulfiram-induced Cocaine Abstinence: Antabuse and Cocaine Relapse

Effect of chronic DBH inhibition on dopamine transmission. Genetic DBH inhibition, and presumably pharmacological DBH inhibition by disulfiram, leads to decreased norepinephrine synthesis in the locus coeruleus and brainstem and norepinephrine release in the midbrain. Because midbrain dopaminergic neurons require noradrenergic drive for normal burst firing and neurotransmitter release, dopamine release is decreased and a compensatory upregulation of high-affinity state dopamine receptors ensues, resulting in behavioral hypersensitivity to psychostimulants.