The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys

Abstract

Rationale Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats. Objective This study examined the effect of cocaine self-administration on behavioral indices of sleep, and alternatively the effect of sleep disruption on cocaine-maintained responding by rhesus monkeys. Methods Seven adult rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a concurrent choice paradigm with food (three 1.0-g pellets) and cocaine (0.003–0.3 mg/kg) or saline presentation. For each monkey the lowest preferred dose of cocaine (> 80% cocaine choice) was determined. Activity data were analyzed during lights out (2000-0600) to determine sleep efficiency, sleep latency and total activity counts. Subsequently, the monkeys were sleep disrupted (awaken every hour during lights-out period) the night prior to food-cocaine choice sessions. Results Self-administration of the preferred dose of cocaine resulted in a significant decrease in sleep efficiency, with a significant increase in total lights-out activity. Sleep disruption significantly altered behavioral indices of sleep, similar to those seen following cocaine self-administration. However, sleep disruption did not affect cocaine self-administration under concurrent choice conditions. Conclusions Based on these findings, cocaine self-administration does appear to disrupt behavioral indices of sleep, although it remains to be determined if treatments that improve sleep measures can affect future cocaine taking.

Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys

“…The present findings support earlier work (Brutcher and Nader 2013) indicating that variables that affect cocaine-induced changes in sleep do not necessarily affect cocaine self-administration. While the choice paradigm provides an index of reinforcing strength that is sensitive to recent pharmacological and environmental manipulations (Banks and Negus 2012), it may be a less sensitive baseline for studying variables that disrupt sleep compared to simple schedules of reinforcement.…”

“…Seven adult (age 16–18) male rhesus monkeys ( Macaca mulatta ) with an extensive behavioral history (Hamilton et al 2010, 2011) including cocaine self-administration under a concurrent cocaine-food choice paradigm (Brutcher and Nader 2013) served as subjects. Monkeys were weighed weekly and healthy body weights were maintained (determined by veterinary staff and somewhat less than free-feeding weights) by food earned during experimental sessions and by supplemental feeding of LabDiet Monkey Chow and fresh fruit no sooner than 30 minutes after the session; water was available ad libitum in the home cage.…”

“…For quantification of sleep measures data were downloaded and analyzed using Actiware Sleep 3.4 (Mini-Matter Co. Inc., Bend, OR) software. Sleep efficiency, defined as total sleep time as a percentage of the period of time with the lights out (600 min) was examined for both acute and chronic quetiapine treatment, as was total nighttime activity (see Brutcher and Nader 2013 for more details).…”

“…Thus, the purpose of the present study was to examine the effects of acute and chronic quetiapine, administered via the oral route, in monkeys self-administering cocaine in the context of an alternative non-drug reinforcer. In addition, this self-administration paradigm has been shown to significantly affect sleep efficiency in monkeys (Brutcher and Nader 2013); if quetiapine, unlike other antipsychotics, is effective in decreasing cocaine choice, the mechanism may be due to the ability of quetiapine to influence several behavioral indices of sleep in monkeys. Similarities in sleep architecture between rhesus monkeys and humans make them an excellent model for studying human sleep (Daley et al 2006).…”

Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys

“…Ten (four females used in experiment 1 and six males used in experiment 2) individually housed adult (ages 16-18) rhesus monkeys (Macaca mulatta) with extensive experimental histories, including .5 years of cocaine self-administration (Hamilton et al, 2010(Hamilton et al, , 2011Brutcher and Nader, 2013), served as subjects. Monkeys were weighed weekly, and body weights were maintained at approximately 98% of free-feeding weights by food earned during experimental sessions and by supplemental feeding of LabDiet Monkey Chow (LabDiet, St. Louis, MO) and fresh fruit no sooner than 30 minutes after the session; water was available ad libitum while in the home cage.…”