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Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment

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An Erratum to this article was published on 07 March 2006

Abstract

Rationale

There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration.

Objectives

The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo.

Methods

CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment.

Results

Mean percentage changes in GABA levels were as follows: pramipexole +17.0±28.0%, venlafaxine +13.0±11.0%, and placebo −2.1±19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites.

Conclusions

This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.

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Acknowledgements

This study was supported, in part, by grants from: the National Institute of Drug Abuse (DA09448 and DA15116 to PFR, DA50038 to DAC); the National Institute on Alcohol Abuse and Alcoholism (K23AA13149 to CCS); and the VA Career Development Award to C.C.S. This experiment complied with the current laws of the USA in which it was performed.

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Authors and Affiliations

  1. Division of Psychiatry, Boston University School of Medicine, Boston, MA, USA

    Chris C. Streeter, Ofra Sarid-Segal, Clifford Knapp, Tae Kwak, Perry F. Renshaw & Domenic A. Ciraulo

  2. Boston VA Healthcare System, Boston, MA, USA

    Chris C. Streeter, Ofra Sarid-Segal, Angela A. Meyer & Domenic A. Ciraulo

  3. McLean Hospital, Belmont, MA, USA

    Chris C. Streeter, John Hennen, Yong Ke, J. Eric Jensen, Leanne E. Nassar & Perry F. Renshaw

  4. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Chris C. Streeter, John Hennen, Yong Ke, J. Eric Jensen, Perry F. Renshaw & Domenic A. Ciraulo

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  1. Chris C. Streeter
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  2. John Hennen
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  3. Yong Ke
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  11. Domenic A. Ciraulo
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Correspondence to Chris C. Streeter.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-005-0236-8

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Streeter, C.C., Hennen, J., Ke, Y. et al. Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment. Psychopharmacology 182, 516–526 (2005). https://doi.org/10.1007/s00213-005-0121-5

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