Nicotine-induced enhancement of Pavlovian alcohol-seeking behavior in rats
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Nicotine enhances responding elicited by Pavlovian cues that predict positive outcomes.
We tested the hypothesis that nicotine acting at nicotinic acetylcholine receptors (nAChRs) would augment Pavlovian alcohol-seeking.
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.
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.
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.
KeywordsPavlovian conditioned approach Ethanol Goal-tracking Mecamylamine
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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