Varenicline effects on cocaine self administration and reinstatement behavior

Behav Pharmacol. 2010 Mar;21(2):96-103. doi: 10.1097/FBP.0b013e328336e9c5.

Abstract

This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion). Thereafter, daily SA sessions continued as before except that every fourth session was preceded by a presession injection of varenicline (0.0, 0.3, 1.0 and 2.0 mg/kg, SC, 50-min presession). In three reinstatement experiments, animals were exposed sequentially to SA training, extinction training, and several reinstatement test sessions. In two of the reinstatement experiments, cocaine-seeking was reinstated by presentation of cocaine-predictive cues at the onset of the test session (cue reinstatement). In a third reinstatement experiment, cocaine-seeking was reinstated by a presession injection of cocaine (drug reinstatement). Each reinstatement session was preceded by an injection of either vehicle or varenicline (dose range of 0.1-2.0 mg/kg). The SA and reinstatement experiments showed that low-dose varenicline decreases reinstatement behavior, without significantly affecting cocaine SA. In contrast, high-dose varenicline increases reinstatement of cocaine-directed behavior and decreases cocaine SA. A control study showed that sucrose-directed behavior is unaltered by varenicline. On the basis of these findings, low-varenicline doses might decrease relapse in cocaine-addicted individuals, but high doses of varenicline might have the opposite effect.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Addictive / drug therapy*
  • Benzazepines / therapeutic use*
  • Cocaine / administration & dosage
  • Cocaine / antagonists & inhibitors*
  • Conditioning, Operant / drug effects
  • Cues
  • Extinction, Psychological / drug effects
  • Male
  • Nicotinic Agonists / therapeutic use*
  • Quinoxalines / therapeutic use*
  • Rats
  • Rats, Long-Evans
  • Secondary Prevention*
  • Self Administration
  • Varenicline

Substances

  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Cocaine
  • Varenicline