Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats

Psychopharmacology (Berl). 2009 Sep;206(1):109-20. doi: 10.1007/s00213-009-1584-6. Epub 2009 Jun 10.

Abstract

Rationale: Escalated, binge-like patterns of cocaine self-administration are engendered by repeated, intermittent exposure to episodes of social defeat stress, as well as by extended drug access.

Objectives: The present study investigated if prior exposure to brief episodes of social defeat stress would intensify the escalation of cocaine self-administration associated with extended access conditions. The consequences of both stress sensitization and prolonged access were further assessed with progressive ratio (PR) break points and during a 24-h variable dose "binge".

Methods: Male Long-Evans rats were exposed to four episodes of defeat stress (days 1-4-7-10), and their locomotor response to cocaine was assessed 10 days later. Rats were subsequently implanted with intravenous catheters. After acquisition, stressed and control rats were allowed daily short (1 h/day) or extended (6 h/day) sessions of cocaine self-administration for 14 days (0.75 mg/kg/infusion). In sequence, we determined break points for cocaine on PR tests and assessed drug intake patterns during a 24-h variable dose binge.

Results: Defeat stress induced cross-sensitization to a cocaine challenge, increased break points for cocaine, and produced persistent, escalated cocaine taking during a 24-h binge. Rats with extended access to cocaine-both stressed and controls-similarly escalated their drug intake throughout the 14 days. Extended access conditions accelerated the rate of cocaine self-administration in the first half of the binge, indicated by shorter post-infusion intervals, but failed to amplify the accumulated drug intake in non-stressed controls.

Conclusions: Both social defeat stress and drug access conditions may engender escalated cocaine intake via distinct mechanisms that regulate drug self-administration.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Addictive / psychology*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology
  • Cocaine / administration & dosage*
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / psychology*
  • Dominance-Subordination*
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Injections, Intravenous
  • Male
  • Models, Animal
  • Motor Activity / drug effects
  • Narcotics / pharmacology
  • Rats
  • Rats, Long-Evans
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Self Administration
  • Social Behavior
  • Stress, Psychological / psychology*

Substances

  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Narcotics
  • Cocaine
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