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Nicotine-induced enhancement of Pavlovian alcohol-seeking behavior in rats

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Abstract

Rationale

Nicotine enhances responding elicited by Pavlovian cues that predict positive outcomes.

Objectives

We tested the hypothesis that nicotine acting at nicotinic acetylcholine receptors (nAChRs) would augment Pavlovian alcohol-seeking.

Methods

Male, Long-Evans rats with unrestricted access to food and water were acclimated to drinking 15% ethanol in their home cages and then given Pavlovian conditioning sessions in which each trial of a 15-s conditioned stimulus (CS, 12 trials/session) was paired with 0.2 ml of ethanol (unconditioned stimulus, US, 2.4 ml/session). Entries into a port where ethanol was delivered were used to assess conditioning. Control groups received explicitly unpaired trials of the CS and US. In experiment 1, systemic injections of saline (1 ml/kg) or nicotine (0.4 mg/kg, freebase) were administered before each session. In experiments 2 and 3, an identical regimen of saline or nicotine injections was administered before the start of Pavlovian conditioning sessions.

Results

All paired groups acquired conditioned port-entry responding to the CS, indicative of Pavlovian alcohol-seeking, whereas unpaired control group did not. Pre-session nicotine injections increased CS port-entries relative to saline, only in the paired group. This nicotine-induced enhancement of Pavlovian alcohol-seeking was blocked by pre-treatment with the nAChR antagonist mecamylamine. Prior exposure to nicotine did not influence the subsequent acquisition of Pavlovian alcohol-seeking.

Conclusions

These findings highlight for the first time that nicotine acting at nAChRs augments Pavlovian alcohol-seeking, specifically in non-restricted rats. Individuals who smoke and drink may thus be particularly susceptible to alcohol cues that could trigger further drinking.

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Acknowledgements

A Nouveau Chercheur award (N.C.) from Fonds de la recherche du Québec—Santé (FRQS) funded this research. N.C. is the recipient of an FRQS Chercheur-Boursier Junior 1 award and a member of the Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementale (CSBN/GRNC). J-M.M. received funding from CSBN/GRNC, Concordia University and the Natural Sciences and Engineering Research Council (NSERC; N.C.). The authors would like to thank Stephen Cabilio for assistance with Med-PC programming and data extraction and Sabrina Heffernan, Angela Ortiz, Tracy Rothwell, and Chandra Srey for assistance with experiments.

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  1. Department of Psychology, Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementale, Concordia University, 7141 Sherbrooke Street West, Room SP 244, Montreal, QC, H4B-1R6, Canada

    Jean-Marie N. Maddux & Nadia Chaudhri

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  1. Jean-Marie N. Maddux
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  2. Nadia Chaudhri
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Correspondence to Nadia Chaudhri.

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Jean-Marie Maddux is now at the Department of Psychology, Lake Forest College, Lake Forest, IL, USA.

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Maddux, JM.N., Chaudhri, N. Nicotine-induced enhancement of Pavlovian alcohol-seeking behavior in rats. Psychopharmacology 234, 727–738 (2017). https://doi.org/10.1007/s00213-016-4508-2

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