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Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor

Nature volume 393, pages 175–178 (1998)Cite this article

Abstract

There is increasing evidence that genetic factors can influence individual differences in vulnerability to drugs of abuse1,2. Serotonin (5-hydroxytryptamine, 5-HT), acting through many receptors can modulate the activity of neural reward pathways and thus the effects of various drugs of abuse3,4,5,6,7,8. Here we examine the effects of cocaine in mice lacking one of the serotonin-receptor subtypes, the 5-HT1B receptor9. We show that mice lacking 5-HT1B display increased locomotor responses to cocaine and that they are more motivated to self-administer cocaine. We propose that even drug-naive 5-HT1B-knockout mice are in a behavioural and biochemical state that resembles that of wild-type mice sensitized to cocaine by repeated exposure to the drug. This altered state might be responsible for their increased vulnerability to cocaine.

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Figure 1: Self-administration behaviour.
Figure 2: Effects of cocaine on open field behaviour.
Figure 3: Basal FRAs in WT (+/+) and KO (−/−) mice.
Figure 4: Basal AP-1 DNA-binding activity in striatal samples.

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Acknowledgements

We thank E. Gardner and J. Chen for biochemical characterization of the mice, R. Aton for help with self-administration studies, and R. Yarmolinksy for help with preparation of the figures. This work was supported by grants from NIDA, Bristol-Meyers, and a HHMI predoctoral fellowship (K.S.-L.)

Author information

Author notes

  1. John C. Crabbe

    Present address: Department of Veterans Affairs Medical Center and Oregon Health Sciences University, Portland, 97201, Oregon, USA

  2. José J. Lucas

    Present address: Centro Biologa Molecular Severo Ochoa CBMSO/CSIC, Universidad Autonoma Madrid, Cento Blanco Madrid 28049, Spain

  3. Noboru Hiroi

    Present address: Laboratory of Molecular Psychobiology, Department of Psychiatry and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA

  4. Nathalie Castanon

    Present address: INSERM, Institute Franois Magendic, 33077, Bordeaux, France

  5. Beatriz A. Rocha, Kimberly Scearce-Levie, Noboru Hiroi and Eric J. Nestler: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, 76107, Texas, USA

    Beatriz A. Rocha

  2. Center for Neurobiology and Behavior, Columbia University, 722 W. 168th Street, P.I. Annex 731, New York, 10032, New York, USA

    Kimberly Scearce-Levie, José J. Lucas, Nathalie Castanon & René Hen

  3. Laboratory of Molecular Psychiatry, Yale University School of Medicine, New Haven, 06508, Connecticut, USA

    Noboru Hiroi & Eric J. Nestler

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Correspondence to René Hen.

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Rocha, B., Scearce-Levie, K., Lucas, J. et al. Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor. Nature 393, 175–178 (1998). https://doi.org/10.1038/30259

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