title: Sleep is differently modulated by basal forebrain GABA(A) and GABA(B) receptors.
abstract: There is evidence that GABA plays a major role in sleep regulation. GABA(A) receptor agonists and different compounds interacting with the GABA(A) receptor complex, such as barbiturates and benzodiazepines, can interfere with the sleep/wake cycle. On the other hand, there is very little information about the possible role of GABA(B) receptors in sleep modulation. The nucleus basalis of Meynert (NBM), a cholinergic area in the basal forebrain, plays a pivotal role in the modulation of sleep and wakefulness, and both GABA(A) and GABA(B) receptors have been described within the NBM. This study used unilateral infusions in the NBM to determine the effects of 3-hydroxy-5-aminomethylisoxazole hydrobromide (muscimol hydrobromide, a GABA(A) receptor subtype agonist) and beta-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen, a GABA(B) receptor subtype agonist) on sleep parameters in freely moving rats by means of polygraphic recordings. Muscimol (0.5 nmol) and baclofen (0.7 nmol) induced an increase in slow-wave sleep and an inhibition of wakefulness. Muscimol, but not baclofen, also caused a decrease in desynchronized sleep parameters. The results reported here indicate that 1) the NBM activation of both GABA(A) and GABA(B) receptors influences the sleep/wake cycle, and 2) GABA(A) but not GABA(B) receptors are important for desynchronized sleep modulation, suggesting that the two GABAergic receptors play different roles in sleep modulation.
authors.affiliation: Istituto di Fisiologia Umana II, Università degli Studi, 20133 Milano, Italy. alfredi.manfridi@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Manfridi
authors.forename: D
authors.initials: D
authors.lastname: Brambilla
authors.forename: M
authors.initials: M
authors.lastname: Mancia
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D020532:Basal Nucleus of Meynert / Q000502:physiology*; D004569:Electroencephalography; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D018755:GABA Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D001418:Baclofen