title: Blockade of the NMDA and AMPA/kainate receptors in the dorsal raphe nucleus prevents the 5-HT₃ receptor agonist m-chlorophenylbiguanide-induced suppression of REM sleep in the rat.
abstract: The effects of the selective 5-HT(3) receptor agonist m-chlorophenylbiguanide (m-CPBG), and of the NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate)/kainate antagonists AP-5 [(±)-2-amino-5-phosphono-pentanoic acid] and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), respectively, were studied in adult male Wistar rats implanted for chronic sleep recordings. The compounds were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of m-CPBG (2 and 4mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Local infusion of AP-5 (0.5-1 mM) and CNQX (2 mM) significantly increased slow wave sleep (SWS). Pretreatment with AP-5 (0.5 mM) or CNQX (0.5 mM) antagonized the m-CPBG-induced suppression of REMS. It is proposed that the reduction of REMS after microinjection of m-CPBG into de DRN is related to the activation of glutamatergic interneurons that express the 5-HT(3) receptor and make synaptic contacts with serotonergic cells. The resultant increase of serotonin release at postsynaptic sites involved in the induction of REMS would provoke the suppression of the behavioral state. Our findings provide, in addition, new details concerning the pharmacology of DRN serotonergic neurons in the rat that may become relevant to the development of drugs for enhancing cortical and subcortical serotonergic neurotransmission.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo 11600, Uruguay. jmonti@mednet.org.uy
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Monti
authors.forename: Héctor
authors.initials: H
authors.lastname: Jantos
authors.forename: Valentina
authors.initials: V
authors.lastname: Catenaccio
authors.forename: Silvia
authors.initials: S
authors.lastname: Xavier
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012892:Sleep Deprivation; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001645:Biguanides; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D018092:Kainic Acid Receptors; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C065734:1-(3-chlorophenyl)biguanide