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The serotonin2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination

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Abstract

Rationale

There is evidence that serotonin2C (5-HT2C) receptors can modulate some behavioural effects of nicotine, but the generality of this action is not known.

Objective

To analyse the influence of the 5-HT2C agonist Ro-60-0175 on responses to nicotine in the five-choice serial reaction time task (5-CSRTT) and on its discriminative stimulus effect; these procedures constitute models for attention-enhancing and subjective effects of nicotine, respectively.

Materials and methods

In the 5-CSRTT, rats were trained to obtain food reinforcers by detecting light stimuli and then challenged with Ro-60-0175 (0.3–0.8 mg/kg) and nicotine (0.2 mg/kg). For drug discrimination studies, rats were trained to discriminate nicotine (0.2 mg/kg) from saline in a two-lever procedure using a tandem schedule of food reinforcement.

Results

In the 5-CSRTT, nicotine positively influenced most response indices, confirming previous results. Ro-60-0175 increased response latencies and omission errors and reduced anticipatory responding but had little effect on response accuracy; importantly, it counteracted the effects of nicotine on response speed and omission errors. Pentobarbitone (10–14 mg/kg) also slowed performance of the 5-CSRTT but did not weaken the nicotine-induced enhancement of performance. In the drug discrimination procedure, Ro-60-0175 was not generalised with nicotine but shifted the nicotine dose–response curve to the right in a dose-related manner.

Conclusions

The data suggest that selective occupancy of 5-HT2C receptors can attenuate some effects of nicotine in the 5-CSRTT and weaken the nicotine discriminative stimulus; these effects cannot be explained by a sedative action of Ro-60-0175.

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Acknowledgements

We gratefully thank the European Union and Medical Research Council for financial support and F. Hoffmann-La Roche, Basel, Switzerland for kindly donating Ro-60-0175. Ian Stolerman was a member of the External Scientific Staff of the Medical Research Council. Britta Hahn kindly provided insightful comments on an earlier version of this report. There are no relevant financial interests to disclose, or a conflict of interest of any kind. The experiments comply with the laws of the UK.

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  1. Davide Quarta

    Present address: Drug Dependence and Behavioural Neurochemistry Department, Psychiatry-CEDD, Medicines Research Centre, GlaxoSmithKline S.p.A., Via Fleming 4, 37135, Verona, Italy

Authors and Affiliations

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

    Davide Quarta, Christopher G. Naylor & Ian P. Stolerman

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  1. Davide Quarta
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  2. Christopher G. Naylor
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Correspondence to Ian P. Stolerman.

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Quarta, D., Naylor, C.G. & Stolerman, I.P. The serotonin2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination. Psychopharmacology 193, 391–402 (2007). https://doi.org/10.1007/s00213-007-0802-3

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