Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms.
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.
Paine
Tracie A
TA
Department of Psychology, Queen's University, Kingston, Canada ON, K7L 3N6.
Dringenberg
Hans C
HC
Olmstead
Mary C
MC
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000009:adverse effects*; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004594:Electrophysiology; D007175:Impulsive Behavior / Q000139:chemically induced*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine