Restoration of Rapid-Eye Movement Sleep During Cocaine Abstinence Reduces Incubation of Cocaine Seeking and Normalizes Dopamine Transporter Function

Abstract

Progressive increases in cocaine craving or seeking during abstinence from cocaine are thought to contribute to relapse. Recent observations suggest that sleep disruptions during abstinence from cocaine may have a significant influence on cocaine seeking. While the neural mechanisms underlying the association between sleep disruptions and increases in cocaine seeking during abstinence continue to be investigated, alterations in mesolimbic dopamine transmission may be a common factor. In these studies, we assessed whether sleep disruptions during abstinence are associated with incubation of cocaine seeking and dopamine terminal adaptations in the nucleus accumbens core of female and male rats. We observed that intermittent access to cocaine followed by abstinence reduced rapid-eye movement sleep, intensified cue-induced cocaine seeking, and enhanced dopamine uptake and dopamine transporter sensitivity to cocaine. Notably, a sleep restoration procedure that restricted sleep to the light phase (active period) restored rapid-eye movement sleep, prevented incubation of cocaine seeking, and normalized baseline dopamine uptake and dopamine transporter sensitivity to cocaine. These findings indicate that rapid-eye movement sleep disruptions during abstinence contribute to exaggerated cocaine seeking and that dopamine transporter adaptations are a potential molecular substrate through which these changes occur. Thus, interventions that restore sleep during cocaine abstinence may serve as effective behavioral therapies for reducing cocaine craving and preventing subsequent relapse.