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.