High cocaine dosage decreases neurogenesis in the hippocampus and impairs working memory

Addict Biol. 2011 Apr;16(2):251-60. doi: 10.1111/j.1369-1600.2010.00241.x. Epub 2010 Aug 23.

Abstract

Drug addiction is a chronic brain disorder, characterized by the loss of the ability to control drug consumption. The neurobiology of addiction is traditionally thought to involve the mesocorticolimbic system of the brain. However, the hippocampus has received renewed interest for its potential role in addiction. Part of this attention is because of the fact that drugs of abuse are potent negative regulators of neurogenesis in the adult hippocampus and may as a result impair learning and memory. We investigated the effects of different dosages of contingent cocaine on cell proliferation and neurogenesis in the dentate gyrus of the hippocampus and on working memory during abstinence, using the water T-maze test, in adult rats. We found that cocaine, in addition to the changes it produces in the reward system, if taken in high doses, can attenuate the production and development of new neurons in the hippocampus, and reduce working memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Central Nervous System Stimulants / toxicity*
  • Cocaine / toxicity*
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiopathology
  • Dopamine Uptake Inhibitors / toxicity*
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory, Short-Term / drug effects*
  • Memory, Short-Term / physiology
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Cocaine