Sub-chronic low dose γ-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine

• Published in: Psychopharmacologia 2003-07, Vol.168 (3), p.339-343
• Main Authors: SCHIFFER, Wynne K, MARSTELLER, Douglas, DEWEY, Stephen L
• Format: Article
• Language: English
• Subjects: 4-Aminobutyrate Transaminase - antagonists & inhibitors; Addictive behaviors; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Cocaine - pharmacology; Cocaine-Related Disorders - drug therapy; Dopamine - metabolism; Dose-Response Relationship, Drug; Drug addiction; Male; Medical sciences; Microdialysis; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Time Factors; Vigabatrin - administration & dosage; Vigabatrin - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-003-1446-6

gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.