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- W65751472 abstract "Disulfiram (Antabuse) has recently shown promise as a pharmacotherapy for cocaine dependence, though the mechanisms underlying its efficacy are unclear. One of the many biochemical actions of disulfiram is inhibition of dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine (NE); consequently, disulfiram reduces brain NE levels. Noradrenergic signaling is required for reinstatement of drug seeking in rats, a paradigm which is thought to model drug relapse. We therefore hypothesized that DBH inhibition underlies the therapeutic effects of disulfiram. To test this hypothesis, cocaine self-administration studies were conducted in rats (N=5–8 per group) given pretreatments of vehicle, disulfiram (100 mg/kg i.p.) or the selective DBH inhibitor nepicastat (50 mg/kg i.p.). We found that neither disulfiram nor nepicastat altered lever pressing behavior during the maintenance phase of self-administration. In contrast, both drugs blocked cocaine-primed reinstatement of lever pressing following extinction. These results suggest that pharmacological DBH inhibition may be an effective treatment for cocaine dependence, potentially by preventing relapse." @default.
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- W65751472 date "2010-04-01" @default.
- W65751472 modified "2023-10-18" @default.
- W65751472 title "Pharmacological inhibition of dopamine beta‐hydroxylase blocks cocaine‐induced reinstatement in rats" @default.
- W65751472 doi "https://doi.org/10.1096/fasebj.24.1_supplement.765.14" @default.
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