title: Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys.
abstract: Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT2Creceptor agonist, WAY163909, and a 5-HT2Areceptor antagonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT2Creceptor and antagonists at the 5-HT2Areceptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY.
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Maylen
authors.initials: M
authors.lastname: Perez Diaz
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.|Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.affiliation: Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Drug Abuse, Rockville, MD, USA.
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Howell
mesh_terms: D056044:Actigraphy / Q000379:methods*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D012646:Self Administration; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D008694:Methamphetamine