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Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates

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Abstract

Rationale

Recent reports have demonstrated that gamma-aminobutyric acid (GABA)-ergic compounds attenuate the reinforcing effects of cocaine in rats. Baclofen, a GABAB receptor agonist, appears to be particularly effective in this respect, suggesting that GABAB receptor activation is critically involved in mediating anti-cocaine effects. Amphetamine, like cocaine, is a psychomotor stimulant with high abuse potential in humans.

Objectives

The purpose of the present investigation was to determine whether baclofen may attenuate the reinforcing effects of d-amphetamine (dAMPH) in rats. Dose–response curves were generated to examine the effect of three doses of baclofen (1.8, 3.2 or 5.6 mg/kg, IP) on dAMPH intravenous self-administration (IVSA). Separate groups were trained to self-administer two doses of dAMPH (0.1 mg/kg or 0.2 mg/kg per injection) under either a fixed-ratio (FR) or progressive ratio (PR) schedule of reinforcement. Microdialysis was performed in an additional group of rats to examine the effect of baclofen on dAMPH-induced increases in dopamine (DA) efflux in the nucleus accumbens (NAc).

Results

Pretreatment with baclofen produced dose-dependent reductions in responding for dAMPH under both the FR and PR schedules, and attenuated dAMPH-induced increases in DA levels in the NAc.

Conclusion

These results add to previous findings showing that baclofen attenuates the reinforcing effects of psychostimulant drugs, and suggest that further investigation into the effects of GABAB receptor agonists on drug self-administration is warranted.

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Acknowledgements

This research was funded by a grant from the Canadian Institutes for Health Research (CIHR) to A.G.P. and a CIHR postdoctoral fellowship to K.B. The authors wish to thank K.S. for microdialysis and HPLC technical support.

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  1. Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada

    Karen Brebner, Soyon Ahn & Anthony G. Phillips

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  1. Karen Brebner
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Correspondence to Karen Brebner.

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Brebner, K., Ahn, S. & Phillips, A.G. Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates. Psychopharmacology 177, 409–417 (2005). https://doi.org/10.1007/s00213-004-1968-6

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  • DOI: https://doi.org/10.1007/s00213-004-1968-6

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