The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Psychopharmacology (Berl). 2016 Aug;233(15-16):2985-97. doi: 10.1007/s00213-016-4341-7. Epub 2016 Jun 9.

Abstract

Rationale: Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug.

Objectives: To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue.

Methods: Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue.

Results: Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement.

Conclusions: Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.

Keywords: Acetylcholine receptor; Alcoholism; Attention; Autoshaping; Behavioral pharmacology; Drinking; Drug addiction; Goal-tracking; Mesolimbic dopamine; Motivation; Pavlovian conditioned approach; Sign-tracking; Smoking.

MeSH terms

  • Animals
  • Central Nervous System Depressants / pharmacology*
  • Conditioning, Classical*
  • Cues
  • Drug-Seeking Behavior / drug effects*
  • Ethanol / pharmacology*
  • Food
  • Male
  • Motivation
  • Nicotine / administration & dosage*
  • Nicotine / pharmacology
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology
  • Reward
  • Self Administration

Substances

  • Central Nervous System Depressants
  • Nicotinic Agonists
  • Ethanol
  • Nicotine