Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine
โ Scribed by Madina R. Gerasimov; Charles R. Ashby Jr.; Eliot L. Gardner; Mark J. Mills; Jonathan D. Brodie; Stephen L. Dewey
- Book ID
- 102656800
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 781 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0887-4476
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โฆ Synopsis
We examined the acute effect of the irreversible GABA-transaminase inhibitor, gamma-vinyl GABA (GVG, Sabril , Vigabatrin ) on increases in nucleus accumbens (NAc) dopamine (DA) following acute administration of methamphetamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose-dependent increase (2,700%) in NAc DA. GVG preadministration (300 or 600 mg/kg), however, inhibited this response by approximately 39 and 61%, respectively. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1,700%. This response was inhibited to a similar extent (44%) regardless of the GVG dose preadministered (300 or 600 mg/kg). In addition, heroin-induced increases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the dose necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol-induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Taken with our previous findings using nicotine or cocaine as the challenge drug, these results indicate that GVG attenuates increases in NAc DA by a mechanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following challenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site.
๐ SIMILAR VOLUMES
Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-induced increases in dopamine (DA) concentrations in both the rodent and primate brain. Furthermore, it abolishes cocaine self-administration and conditioned place preference, while having no effect