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Tolerance to nicotine in mice lacking α7 nicotinic receptors

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Abstract

Rationale

Previous studies have suggested that a knockout of the gene coding for α7 nicotinic receptor subunits influences the behaviour of undrugged mice but not the acute effect of nicotine on locomotor activity.

Objectives

The present studies extend these observations to nicotine tolerance assessed by means of schedule-controlled behaviour.

Methods

Groups of α7−/− and α7+/+ mice were trained to press levers under an FR20 schedule of food reinforcement. The acute response rate-depressant effects of nicotine were determined in both genotypes and the mice were then subdivided into groups treated daily with nicotine (1.2 mg/kg/day) or saline. After 39 days of exposure to this regimen, the dose–response curves were re-determined.

Results

Knockout of the α7 gene had no consistent effect on the lever-pressing behaviour of undrugged mice and did not influence the acute, dose-related, response rate-depressant effect of nicotine (0.2–1.2 mg/kg). When dose–response curves for nicotine (0.4–2.0 mg/kg) were re-determined after daily dosing with the drug, both wild-type and knockout mice developed similar tolerance to nicotine, as shown by ∼2.5-fold shifts to the right of the dose–response curves.

Conclusions

Nicotinic receptors containing the α7 subunit do not play a significant role in the regulation of the lever-pressing behaviour studied or in the acute behavioural depressant effect of nicotine and the development of tolerance to that effect. Such results contrast with previous reports suggesting profound impairments in sensitivity to nicotine in nicotinic receptor β2−/− mice.

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Acknowledgements

We thank Swital Patel for assistance with some of the experiments and the European Union and the Medical Research Council for financial support.

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Authors and Affiliations

  1. Section of Behavioural Pharmacology, Institute of Psychiatry P049, King’s College London, London, SE5 8AF, UK

    C. Naylor, D. Quarta & I. P. Stolerman

  2. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, UK

    C. Fernandes

Authors
  1. C. Naylor
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  2. D. Quarta
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  3. C. Fernandes
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  4. I. P. Stolerman
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Corresponding author

Correspondence to I. P. Stolerman.

Additional information

C. Naylor and D. Quarta are listed alphabetically and contributed equally to the work.

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Naylor, C., Quarta, D., Fernandes, C. et al. Tolerance to nicotine in mice lacking α7 nicotinic receptors. Psychopharmacology 180, 558–563 (2005). https://doi.org/10.1007/s00213-005-2187-5

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  • DOI: https://doi.org/10.1007/s00213-005-2187-5

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