Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats.
Gabapentin is a gamma-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present study, we investigated the effects of gabapentin on intravenous cocaine self-administration and cocaine-triggered reinstatement of drug-seeking behavior, as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We found that gabapentin (25-200 mg/kg, i.p., 30 min or 2 h prior to cocaine) failed to inhibit intravenous cocaine (0.5 mg/kg/infusion) self-administration under a fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine-seeking behavior. In vivo microdialysis showed that the same doses of gabapentin produced a modest increase (approximately 50%, p<0.05) in extracellular NAc GABA levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no effect in the addiction-related animal behavioral models here tested. This is in striking contrast to positive findings in the same animal models shown by another GABAmimetic--gamma-vinyl GABA (see companion piece to present article).
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, United States.
Xiao-Qing
XQ
Peng
Xia
X
Li
Jie
J
Li
P Veeraraghavan
PV
Ramachandran
Pravin D
PD
Gagare
Debarshi
D
Pratihar
Charles R
CR
Ashby
Eliot L
EL
Gardner
Zheng-Xiong
ZX
Xi
D000588:Amines / Q000627:therapeutic use*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000453:epidemiology / Q000534:rehabilitation*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000139:chemically induced*; D004298:Dopamine / Q000378:metabolism*; D000077206:Gabapentin; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D012646:Self Administration; D014662:Vasoconstrictor Agents / Q000009:adverse effects*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
D000588:Amines; D014151:Anti-Anxiety Agents; D003509:Cyclohexanecarboxylic Acids; D014662:Vasoconstrictor Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D003042:Cocaine; D004298:Dopamine