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Reduced sensitivity to reward in CB1 knockout mice

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Abstract

Rationale

Previous studies have demonstrated that the activation and blockade of the cannabinoid type 1 receptor (CB1) leads to an enhancement and decrease of the consumption of food and other orally ingested reinforcers, respectively.

Objective

To gain further knowledge about the role of CB1 in sucrose/saccharin reinforcing efficacy and intake, we tested CB1 knockout (CB1-KO) and littermate wild-type (WT) control mice in several self-administration experimental protocols.

Methods

Operant (fixed or progressive ratio schedule) and non-operant conditioning procedures were used. In addition, a choice analysis based on the “matching law” as well as a microstructural analysis of the intra-session pattern of self-administration was performed.

Results

CB1-KO mice consume less sucrose under operant conditions or when using a two-bottle free choice procedure. Moreover, as revealed by additional behavioural analysis, CB1-KO mice exhibit a decreased sensitivity to the rewarding properties of sucrose. In agreement with this finding, the differences between WT and CB1-KO mice faded away when the palatability of sucrose was devaluated by adding quinine, but not when a non-caloric sweetener, saccharin, was available.

Conclusions

These results demonstrate a modulatory role of CB1 in the determination of the rewarding properties of sucrose and probably, as suggested by previous studies, other reinforcers.

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Acknowledgements

We thank Dr Margaret Martinetti for her helpful advice in the implementation and interpretation of the matching law procedure and Barbara Wölfel for genotyping. This research was supported by the BMBF grant FKZ 01GS0117 and the European Community through a grant to the TARGALC consortium (QLRT-2001-01048).

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Authors and Affiliations

  1. Department of Psychopharmacology, Central Institute for Mental Health, CIMH, University of Heidelberg, 68159, Mannheim, Germany

    Carles Sanchis-Segura, Brandon H. Cline & Rainer Spanagel

  2. Area de Psicobiologia, Universitat Jaume I, Castello, Spain

    Carles Sanchis-Segura

  3. Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, Munich, Germany

    Giovanni Marsicano & Beat Lutz

Authors
  1. Carles Sanchis-Segura
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  2. Brandon H. Cline
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  3. Giovanni Marsicano
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  4. Beat Lutz
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  5. Rainer Spanagel
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Correspondence to Rainer Spanagel.

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Sanchis-Segura, C., Cline, B.H., Marsicano, G. et al. Reduced sensitivity to reward in CB1 knockout mice. Psychopharmacology 176, 223–232 (2004). https://doi.org/10.1007/s00213-004-1877-8

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  • DOI: https://doi.org/10.1007/s00213-004-1877-8

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