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Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats

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Abstract

Rationale

The cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS).

Objective

We examined the effects of rimonabant and the CB1/2 receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature

Materials and methods

Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003–0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions

Results

Rimonabant blocked nicotine-evoked responding. CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task

Conclusions

The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation.

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Acknowledgments

The authors would like to thank Veronica C. Barra and Kimberly D. Horky for their dedicated assistance with the animals and to thank Dr. Calvin P. Garbin for his statistical assistance. We gratefully recognize the National Institute on Drug Abuse Drug Supply Program for providing the rimonabant and CP 55,940. The research and RA Bevins were partially supported by United States Public Health Service Grant DA018114. JE Murray was supported by DA025399 during the preparation of this manuscript. NR Wells was partially supported by UNL Undergraduate Creative Activities and Research Experiences. None of these organizations had any role in the study design, data collection, analysis, or the interpretation, the writing of the manuscript, or the decision to submit the paper for publication. All MED-PC programs described in this article are available upon request. Correspondence related to this article should be addressed to Rick A. Bevins, Department of Psychology, University of Nebraska-Lincoln, Lincoln NE USA 68588-0308, or e-mail rbevins1@unl.edu.

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  1. Department of Psychology, University of Nebraska—Lincoln, Lincoln, NE, 68588-0308, USA

    Jennifer E. Murray, Nicole R. Wells, George D. Lyford & Rick A. Bevins

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  1. Jennifer E. Murray
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  2. Nicole R. Wells
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Correspondence to Rick A. Bevins.

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Murray, J.E., Wells, N.R., Lyford, G.D. et al. Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats. Psychopharmacology 205, 655–665 (2009). https://doi.org/10.1007/s00213-009-1572-x

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