Stimulation of NMDA and AMPA receptors in the rat nucleus basalis of Meynert affects sleep.
The nucleus basalis of Meynert (NBM), a heterogeneous area in the basal forebrain involved in the modulation of sleep and wakefulness, is rich in glutamate receptors, and glutamatergic fibers represent an important part of the input to this nucleus. With the use of unilateral infusions in the NBM, the effects of two different glutamatergic subtype agonists, namely N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) hydrobromide, on sleep and wakefulness parameters were determined in freely moving rats by means of polygraphic recordings. NMDA (5 nmol) and AMPA (0.4 nmol) induced an increase in wakefulness and an inhibition of slow-wave sleep. AMPA, but not NMDA, also caused a decrease in desynchronized sleep. These AMPA- and NMDA-mediated effects were counteracted by a pretreatment with the specific NMDA antagonist 2-amino-5-phosphonopentanoic acid (20 nmol) and the specific AMPA antagonist 6,7-dinitroquinoxaline-2,3-dione (2 nmol), respectively. The results reported here indicate that 1) the NBM activation of both NMDA and AMPA glutamate receptors exert a modulatory influence on sleep and wakefulness, and 2) AMPA, but not NMDA receptors, are involved in the modulation of desynchronized sleep, suggesting a different role for NBM NMDA and non-NMDA receptors in sleep modulation.
Manfridi
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Istituto di Fisiologia Umana II, Università degli Studi, 20133 Milano, Italy.
Brambilla
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D
Mancia
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism*; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid