Diverse effects of GABA-mimetic drugs on cocaine-evoked self-administration and discriminative stimulus effects in rats.
BACKGROUND
Recent data indicate that gamma-aminobutyric acid (GABA) is a modulator of behavioral responses to cocaine.


OBJECTIVE
The efficacy of gabapentin (a cyclic GABA analogue), tiagabine (a GABA reuptake inhibitor), or vigabatrin (an inhibitor of GABA transaminase and reuptake) to alter cocaine-seeking behavior and discriminative effects was examined in rats.


METHODS
Rats were trained to press a lever for cocaine (0.5 mg/kg per infusion) paired with a cue (light + tone) using a fixed ratio (FR) 5 schedule of reinforcement. After extinction, the cocaine-seeking behavior was reinstated by cocaine priming (10 mg/kg). Another group of rats was trained to discriminate cocaine (10 mg/kg) from saline in a two-lever FR 20 task.


RESULTS
Vigabatrin (150-250 mg/kg) decreased cocaine-maintained responding, whereas tiagabine (10 mg/kg) significantly reduced responses on the "active" lever. Vigabatrin (150-250 mg/kg) significantly decreased responding to the cocaine-priming dose and a nonsignificant attenuation of cocaine-induced reinstatement was seen after tiagabine (5-10 mg/kg). Gabapentin (10-30 mg/kg) failed to alter maintenance of cocaine self-administration or drug-induced reinstatement. Pretreatment with either gabapentin, tiagabine, or vigabatrin resulted in neither reinstatement of cocaine seeking nor alterations in cocaine discrimination.


CONCLUSIONS
Our study demonstrates that vigabatrin (only at the 150 mg/kg dose) exerted inhibitory actions on cocaine-maintained responding and attenuated the reinstatement of extinguishing responding more effectively than gabapentin or tiagabine and with less evidence of motor impairment than the latter drugs. Present findings do not support a role for gabapentin or tiagabine for the possible treatment of cocaine relapse, whereas albeit limited effects of vigabatrin may be seen.
Filip
Małgorzata
M
Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Kraków, Poland. filip@if-pan.krakow.pl
Frankowska
Małgorzata
M
Zaniewska
Magdalena
M
Gołda
Anna
A
Przegaliński
Edmund
E
Vetulani
Jerzy
J
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000077206:Gabapentin; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D000078308:Tiagabine; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D003042:Cocaine; D000078308:Tiagabine