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Diverse effects of GABA-mimetic drugs on cocaine-evoked self-administration and discriminative stimulus effects in rats

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Abstract

Rationale

Recent data indicate that γ-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.

Materials and 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.

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Acknowledgments

We are grateful to Dr. Andrew C. McCreary for the comments and language editing of the manuscript. Expert technical assistance was provided by Ewa Nowak and Karolina Wydra. Gabapentin was kindly donated by Pfizer.

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Authors and Affiliations

  1. Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343, Kraków, Poland

    Małgorzata Filip, Małgorzata Frankowska, Magdalena Zaniewska, Anna Gołda, Edmund Przegaliński & Jerzy Vetulani

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  1. Małgorzata Filip
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  2. Małgorzata Frankowska
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  3. Magdalena Zaniewska
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  4. Anna Gołda
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  5. Edmund Przegaliński
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  6. Jerzy Vetulani
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Corresponding author

Correspondence to Małgorzata Filip.

Additional information

This research was supported by the grant no. 033/P05/2001 from the Ministry of Education and Science (Warsaw, Poland) and by the Institute of Pharmacology, Polish Academy of Sciences (Kraków, Poland).

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Filip, M., Frankowska, M., Zaniewska, M. et al. Diverse effects of GABA-mimetic drugs on cocaine-evoked self-administration and discriminative stimulus effects in rats. Psychopharmacology 192, 17–26 (2007). https://doi.org/10.1007/s00213-006-0694-7

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  • DOI: https://doi.org/10.1007/s00213-006-0694-7

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