High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats

Psychopharmacology (Berl). 2012 Jul;222(1):89-97. doi: 10.1007/s00213-011-2626-4. Epub 2012 Jan 14.


Rationale: Although high anxiety is commonly associated with drug addiction, its causal role in this disorder is unclear.

Objectives: In light of strong evidence for dissociable neural mechanisms underlying heroin and cocaine addiction, the present study investigated whether high anxiety predicts the propensity of rats to lose control over intravenous cocaine or heroin self-administration.

Methods: Sixty-four rats were assessed for anxiety in the elevated plus-maze, prior to extended access to intravenous cocaine or heroin self-administration.

Results: High-anxious rats, identified in the lower quartile of the population, showed a greater escalation of cocaine, but not heroin, self-administration compared with low-anxious rats selected in the upper quartile of the population. Anxiety scores were also positively correlated with the extent of escalation of cocaine self-administration.

Conclusions: The present data suggest that high anxiety predisposes rats to lose control over cocaine-but not heroin-intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / complications
  • Anxiety / physiopathology*
  • Cocaine / administration & dosage*
  • Disease Models, Animal
  • Heroin / administration & dosage*
  • Male
  • Maze Learning
  • Rats
  • Self Administration
  • Substance-Related Disorders / etiology


  • Heroin
  • Cocaine