Journal
PSYCHOPHARMACOLOGY
Volume 240, Issue 4, Pages 871-880Publisher
SPRINGER
DOI: 10.1007/s00213-023-06328-4
Keywords
Sign-tracking; Goal-tracking; Addiction; Rat; Acetylcholine; Pavlovian conditioning; Reward learning; Incentive salience; Scopolamine; Mecamylamine
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Acetylcholinergic antagonists have shown promise in reducing addiction-related behaviors, but the psychological mechanisms behind their effects remain unclear. This study investigates the selective effects of systemic antagonism of acetylcholine receptors on behavior in rats.
RationaleAcetylcholinergic antagonists have shown some promise in reducing addiction-related behaviors in both preclinical and clinical studies. However, the psychological mechanisms by which these drugs are able to affect addictive behavior remain unclear. A particular key process for the development of addiction is the attribution of incentive salience to reward-related cues, which can be specifically measured in animals using a Pavlovian conditioned approach procedure. When confronted with a lever that predicts food delivery, some rats engage with the lever directly (i.e., they sign track), indicating attribution of incentive-motivational properties to the lever itself. In contrast, others treat the lever as a predictive cue and approach the location of impending food delivery (i.e., they goal track), without treating the lever itself as a reward.ObjectivesWe tested whether systemic antagonism of the either nicotinic or muscarinic acetylcholine receptors would selectively affect sign- or goal-tracking behavior, indicating a selective effect on incentive salience attribution.MethodsA total of 98 male Sprague Dawley rats were either given the muscarinic antagonist scopolamine (100, 50, or 10 mu g/kg i.p.) or the nicotinic antagonist mecamylamine (0.3, 1.0, or 3 mg/kg i.p.) before being trained on a Pavlovian conditioned approach procedure.ResultsScopolamine dose-dependently decreased sign tracking behavior and increased goal-tracking behavior. Mecamylamine reduced sign-tracking but did not affect goal-tracking behavior.ConclusionsAntagonism of either muscarinic or nicotinic acetylcholine receptors can reduce incentive sign-tracking behavior in male rats. This effect appears to be specifically due to a reduction in incentive salience attribution since goal-tracking either increased or was not affected by these manipulations.
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