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Minocycline attenuates subjective rewarding effects of dextroamphetamine in humans

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Abstract

Rationale

Minocycline, a tetracycline antibiotic, interacts with brain glutamate and dopamine neurotransmission. In preclinical studies, minocycline attenuated amphetamine-induced acute dopamine release and subsequent behavioral sensitization. The goal of this study was to determine minocycline’s effects on the acute physiological, behavioral, and subjective responses to dextroamphetamine (DAMP) in healthy volunteers.

Methods

Ten healthy volunteers participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects had a 5-day treatment period with either minocycline (200 mg/day) or placebo and then were crossed over for 5 days of the other treatment. After 2 days of taking the study medication, on days 3 and 4, subjects were randomly assigned to double-blind acute challenge with either 20 mg/70 kg DAMP or placebo DAMP (randomly labeled as drug A or B) and then crossed over to the other challenge. On day 5 (experimental session 3), subjects had the opportunity to self-administer either placebo or DAMP capsules by working on a progressive ratio computer task.

Results

Minocycline attenuated DAMP-induced subjective rewarding effects but did not change DAMP choice behavior. Minocycline treatment speeded reaction times on a Go No-Go task and reduced plasma cortisol levels.

Conclusions

These findings warrant further studies examining the potential use of minocycline for stimulant addiction.

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Acknowledgments

This research was supported by the Veterans Administration Mental Illness Research, Education and Clinical Center (MIRECC), and National Institute on Drug Abuse (NIDA) grants P50-DA12762, K05-DA0454 (TK), K02-DA021304 (MS), and K01-DA-019446 (MM).

We would like to thank Ellen Mitchell, R.N. and Stacy Minnix for the technical assistance.

Conflict of interest

Dr. Kosten is in the Speakers Bureau of Reckitt. He served as a consultant for Celtic, Alkermes, Synosia, Catalyst, and Gerson Lerman and has ownership interests with Pfizer and Johnson & Johnson. Dr. Mooney has received research grants from Pfizer. None of the products of these companies are associated with this work. The other authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry and VA Connecticut Healthcare System, School of Medicine, Yale University, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT, 06516, USA

    Mehmet Sofuoglu

  2. Department of Psychiatry, School of Medicine, University of Minnesota, Minneapolis, MN, USA

    Marc Mooney

  3. Baylor College of Medicine, Houston, TX, USA

    Thomas Kosten

  4. Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Andrew Waters

  5. Chiba University Center for Forensic Mental Health, Inohana, Chiba, Japan

    Kenji Hashimoto

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  1. Mehmet Sofuoglu
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  2. Marc Mooney
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  3. Thomas Kosten
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  4. Andrew Waters
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  5. Kenji Hashimoto
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Correspondence to Mehmet Sofuoglu.

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Sofuoglu, M., Mooney, M., Kosten, T. et al. Minocycline attenuates subjective rewarding effects of dextroamphetamine in humans. Psychopharmacology 213, 61–68 (2011). https://doi.org/10.1007/s00213-010-2014-5

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  • DOI: https://doi.org/10.1007/s00213-010-2014-5

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