Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms

Behav Brain Res. 2003 Dec 17;147(1-2):135-47. doi: 10.1016/s0166-4328(03)00156-6.

Abstract

Drug addiction can be considered an impulse control disorder in that addicts exhibit increased impulsivity on both behavioural and self-report measures. We investigated whether chronic cocaine affects delay of gratification and/or behavioural disinhibition in rats using the delayed reinforcement and Go/No-go paradigms. Animals were treated with saline or cocaine (15 mg/kg) three times per day for 14 days; all behavioural tests occurred prior to daily injections. To assess the effectiveness of the cocaine treatment, sucrose intake, behavioural sensitization and serotonin (5-HT)-dependent (dorsal raphe-stimulated) cortical activation were also measured. Chronic cocaine caused a transient (days 7-8) increase in impulsivity in the delayed reinforcement paradigm, but did not influence behaviour in the Go/No-go paradigm. As expected, chronic cocaine increased behavioural sensitization scores, although it did not affect sucrose consumption. Although, cocaine treatment did not affect dorsal raphe-stimulated electrocorticographic activation, the serotonergic receptor antagonist methiothepin (0.1 mg/kg) was more effective in blocking cortical activation in cocaine- than in saline-treated animals. The electrocorticographic changes may be the result of a pre-synaptic 5-HT deficit and the compensatory supersensitivity of post-synaptic 5-HT receptors. Given the differential time courses of the behavioural and electrocorticographic data, however, this change probably does not mediate the effects of chronic cocaine in the delayed reinforcement paradigm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Cerebral Cortex / anatomy & histology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Cerebral Cortex / radiation effects
  • Choice Behavior / drug effects
  • Cocaine / adverse effects*
  • Dopamine Uptake Inhibitors / adverse effects*
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Electrophysiology
  • Impulsive Behavior / chemically induced*
  • Male
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Reinforcement Schedule
  • Reinforcement, Psychology

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine