Single prolonged stress decreases sign-tracking and cue-induced reinstatement of cocaine-seeking

Behav Brain Res. 2019 Feb 1:359:799-806. doi: 10.1016/j.bbr.2018.07.026. Epub 2018 Aug 2.

Abstract

Exposure to prolonged, uncontrollable stress reduces reward-seeking behavior, resulting in anhedonia in neuropsychiatric disorders, such as posttraumatic stress disorder. However, it is unclear to what degree stressed subjects lose interest in rewards themselves or in reward-related cues that instigate reward-seeking behavior. In the present study, we investigated the effects of single prolonged stress (SPS) on cue-directed behavior in two different procedures: Pavlovian conditioned approach (PCA) and cue-induced reinstatement of cocaine-seeking. In Experiment 1, rats were exposed to SPS and tested for the acquisition of sign-tracking (cue-directed) and goal-tracking (reward-directed) behaviors during a PCA procedure. In Experiment 2, rats were exposed to SPS and tested for the expression of sign- and goal-tracking as well as cue-induced reinstatement of cocaine-seeking. Because dopaminergic activity in the nucleus accumbens is known to play a central role in many cue-directed behaviors, including both sign-tracking and cue-induced reinstatement, Experiment 3 used in vivo microdialysis to measure the effect of SPS on baseline and evoked dopamine levels in the nucleus accumbens. SPS decreased sign-tracking and increased goal-tracking during the acquisition of PCA behavior without affecting reward consumption. In addition, SPS decreased cue-induced reinstatement without affecting cocaine self-administration. Finally, SPS decreased evoked but not baseline levels of dopamine in the nucleus accumbens. These results suggest that SPS decreases the motivational, but not consummatory, aspects of reward-seeking behavior, which may result from long-term, SPS-induced reductions in dopamine release in the nucleus accumbens.

Keywords: Anhedonia; Dopamine; Incentive salience; Motivation; Nucleus accumbens; Pavlovian conditioned approach.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Cues*
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Drug-Seeking Behavior / drug effects*
  • Drug-Seeking Behavior / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology*
  • Self Administration
  • Stress, Psychological / physiopathology*
  • Time Factors

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine