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

RATIONALE

gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism.

OBJECTIVES

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).

METHODS

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.

RESULTS

Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose.

CONCLUSIONS

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.