title: Positive allosteric modulation of mGlu7 receptors by AMN082 affects sleep and wakefulness in the rat.
abstract: Evidence indicates that metabotropic glutamate receptors (mGlu) are involved in the regulation of physiological and behavioral processes, and glutamate has been implicated in several pathologies of the Central Nervous System. Pharmacological evidence suggests the therapeutic potential of targeting mGlu7 receptor in a number of pathological conditions; and previous research has shown the involvement of glutamate on sleep and wakefulness regulation. Here, the effects of mGlu7 receptor selective modulation on sleep and wake states are explored. 32 male Wistar rats were implanted with electrodes for recording sleep and wakefulness. N,N'-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) (5, 10, and 20mg/kg, i.p.), a potent, selective and systemically active mGlu7 receptor positive allosteric modulator, or vehicle was administered 1 hour after the beginning of the light period. AMN082 (5 and 10mg/kg) significantly increased total time of sleep; and time spent on Slow Wave Sleep (SWS) was increased. AMN082 at 10mg/kg specifically affected Light SWS, increasing time spent on Light SWS. The highest dose of AMN082, 20mg/kg, significantly reduced time spent in Rapid Eye Movement (REM) sleep, decreasing the number of REM sleep episodes and their mean duration. Total time spent awake was increased and mean episode duration of wakefulness was prolonged. The present results suggest that mGlu7 receptors might be involved in sleep regulation and drugs targeting these receptors could affect sleep and wakefulness architecture.
authors.affiliation: Department of Psychobiology, Faculty of Psychology, Campus de Teatinos s/n, University of Málaga, 29071 Málaga, Spain. mcavas@uma.es
authors.forename: María
authors.initials: M
authors.lastname: Cavas
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Scesa
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Navarro
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology*
chemical_list: D001559:Benzhydryl Compounds; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7