Robert E Brutcher1, Michael A Nader. 1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.
Abstract
RATIONALE: Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse. OBJECTIVE: The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys. METHODS: Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003-0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25-75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14-16 days) quetiapine treatment (25-250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study. RESULTS: Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity. CONCLUSIONS: These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.
RATIONALE: Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse. OBJECTIVE: The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys. METHODS: Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003-0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25-75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14-16 days) quetiapine treatment (25-250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study. RESULTS: Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity. CONCLUSIONS: These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.
Authors: Michael A Nader; Drake Morgan; H Donald Gage; Susan H Nader; Tonya L Calhoun; Nancy Buchheimer; Richard Ehrenkaufer; Robert H Mach Journal: Nat Neurosci Date: 2006-07-09 Impact factor: 24.884
Authors: Peter T Morgan; Edward F Pace-Schott; Zakir H Sahul; Vladimir Coric; Robert Stickgold; Robert T Malison Journal: Addiction Date: 2008-08 Impact factor: 6.526