Transient inactivation of the paraventricular nucleus of the thalamus enhances cue-induced reinstatement in goal-trackers, but not sign-trackers

Psychopharmacology (Berl). 2018 Apr;235(4):999-1014. doi: 10.1007/s00213-017-4816-1. Epub 2017 Dec 28.

Abstract

Rationale: The paraventricular nucleus of the thalamus (PVT) has been shown to mediate cue-motivated behaviors, such as sign- and goal-tracking, as well as reinstatement of drug-seeking behavior. However, the role of the PVT in mediating individual variation in cue-induced drug-seeking behavior remains unknown.

Objectives: This study aimed to determine if inactivation of the PVT differentially mediates cue-induced drug-seeking behavior in sign-trackers and goal-trackers.

Methods: Rats were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their Pavlovian conditioned approach behavior. Rats were then exposed to 15 days of cocaine self-administration, followed by a 2-week forced abstinence period and then extinction training. Rats then underwent tests for cue-induced reinstatement and general locomotor activity, prior to which they received an infusion of either saline (control) or baclofen/muscimol (B/M) to inactivate the PVT.

Results: Relative to control animals of the same phenotype, GTs show a robust increase in cue-induced drug-seeking behavior following PVT inactivation, whereas the behavior of STs was not affected. PVT inactivation did not affect locomotor activity in either phenotype.

Conclusion: In GTs, the PVT appears to inhibit the expression of drug-seeking, presumably by attenuating the incentive value of the drug cue. Thus, inactivation of the PVT releases this inhibition in GTs, resulting in an increase in cue-induced drug-seeking behavior. PVT inactivation did not affect cue-induced drug-seeking behavior in STs, suggesting that the role of the PVT in encoding the incentive motivational value of drug cues differs between STs and GTs.

Keywords: Cocaine; Goal-tracker; Individual variation; Paraventricular nucleus of the thalamus; Reinstatement; Relapse; Reward cue; Sign-tracker.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Cues*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects*
  • Drug-Seeking Behavior / physiology
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Goals*
  • Male
  • Midline Thalamic Nuclei / drug effects*
  • Midline Thalamic Nuclei / physiology
  • Motivation / drug effects
  • Motivation / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine