Exaggerated cue-induced reinstatement of cocaine seeking but not incubation of cocaine craving in a developmental rat model of schizophrenia

Psychopharmacology (Berl). 2013 Mar;226(1):45-51. doi: 10.1007/s00213-012-2882-y. Epub 2012 Sep 26.


Rationale: Patients with schizophrenia exhibit high comorbidity for substance abuse, but the biological underpinnings of this dual-diagnosis condition are still unclear. Previous studies have shown that rats with a neonatal ventral hippocampal lesion (NVHL), a widely used developmental animal model of schizophrenia, exhibit increased cocaine and methamphetamine self-administration and cocaine-induced reinstatement.

Objective: Here, we assessed whether a NVHL would also potentiate cue-induced reinstatement of cocaine seeking and the time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving) in adult rats.

Methods: Rats were trained to self-administer cocaine (3 or 6 h/day with 0.75 mg kg(-1) infusion(-1) paired with a tone-light cue) for 10 days, followed by extinction training (3 h/day) and cue-induced reinstatement of cocaine seeking. Other rats were tested for incubation of cocaine craving, assessed in extinction tests 1 and 30 days after the last self-administration session.

Results: Although there was no significant difference in cocaine intake between NVHL and sham controls, NVHL rats took significantly longer to reach an a priori set extinction criterion and exhibited enhanced cue-induced reinstatement. However, while cue-induced cocaine seeking was higher after 30 days than after 1 day of withdrawal (incubation of cocaine craving), the NVHL had no effect on this incubation.

Conclusion: These data confirm previous reports on enhanced resistance to extinction after NVHL and demonstrate that NVHL rats exhibit enhanced cue-induced reinstatement of cocaine seeking after extinction, a measure of drug relapse.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain Mapping
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / psychology*
  • Cues*
  • Diagnosis, Dual (Psychiatry)
  • Disease Models, Animal*
  • Drug-Seeking Behavior*
  • Extinction, Psychological / drug effects
  • Female
  • Hippocampus / injuries
  • Hippocampus / physiopathology
  • Rats
  • Rats, Long-Evans
  • Schizophrenia* / physiopathology
  • Schizophrenic Psychology
  • Self Administration
  • Substance Withdrawal Syndrome / psychology


  • Cocaine