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Nicotine-induced enhancement of a sensory reinforcer in adult rats: antagonist pretreatment effects

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Abstract

Rationale and objectives

The reinforcement-enhancing effect (REE) of nicotine refers to the drug’s ability to enhance the strength of other primary and conditioned reinforcers. The main aim was to investigate neuropharmacological mechanisms underlying nicotine’s strengthening of a primary visual reinforcer (i.e., a light cue), using a subcutaneous (SC) dose previously shown to provide plasma nicotine levels associated with habitual smoking.

Methods

Adult male rats pressed an “active” lever to illuminate a brief cue light during daily 60-min sessions. Rats that showed a clear REE were tested with systemically administered pretreatment drugs followed by nicotine (0.1 mg/kg SC) or saline challenge, in within-subject counterbalanced designs. Pretreatments were mecamylamine (nicotinic, 0.1-1 mg/kg SC), SCH 39166 (D1-like dopaminergic, 0.003-0.2 mg/kg SC), naloxone (opioid, 1 and 5 mg/kg SC), prazosin (alpha1-adrenergic antagonist, 1 and 2 mg/kg IP), rimonabant (CB1 cannabinoid inverse agonist, 3 mg/kg IP), sulpiride (D2-like dopaminergic antagonist, 40 mg/kg SC), or propranolol (beta-adrenergic antagonist, 10 mg/kg IP).

Results

The nicotine REE was abolished by three antagonists at doses that did not impact motor output, i.e., mecamylamine (1 mg/kg), SCH 39166 (0.01 and 0.03 mg/kg), and naloxone (5 mg/kg). Prazosin and rimonabant both attenuated the nicotine REE, but rimonabant also suppressed responding more generally. The nicotine REE was not significantly altered by sulpiride or propranolol.

Conclusions

In adult male rats, the reinforcement-enhancing effect of low-dose nicotine depends on nicotinic receptor stimulation and on neurotransmission via D1/D5 dopaminergic, opioid, alpha1-adrenergic, and CB1 cannabinoid receptors.

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Acknowledgements

Supported by the Canadian Institutes of Health Research of Canada (operating grant 156045, to P.B.S.C.) and by Undergraduate Student Research Awards to SR and TMVC (the Natural Sciences and Engineering Research Council of Canada and Fonds de la Recherche en Santé du Québec, respectively). P.B.S.C. is a member of the Center for Studies in Behavioral Neurobiology at Concordia University, Montreal. The authors have no financial relationship with the organizations that sponsored this research. All experiments comply with the current laws of Canada.

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  1. Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada

    Doran J. Satanove, Simon Rahman, T. M. Vanessa Chan, Suelynn Ren & Paul B. S. Clarke

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  1. Doran J. Satanove
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  2. Simon Rahman
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  3. T. M. Vanessa Chan
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Correspondence to Paul B. S. Clarke.

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All research procedures were reviewed and approved by the McGill Animal Care Committee in accordance with the guidelines of the Canadian Council on Animal Care.

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Satanove, D.J., Rahman, S., Chan, T.M.V. et al. Nicotine-induced enhancement of a sensory reinforcer in adult rats: antagonist pretreatment effects. Psychopharmacology 238, 475–486 (2021). https://doi.org/10.1007/s00213-020-05696-5

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