title: Two weeks of buspirone protects against posthypoxic ventilatory pauses in the C57BL/6J mouse strain.
abstract: The purpose was to determine if 2 weeks of buspirone suppressed post-hypoxic breathing instability and pauses in the C57BL/6J (B6) mouse. Study groups were vehicle (saline, n=8), low-dose (1.5 mg/kg, n=8), and high-dose buspirone (5.0 mg/kg, n=8). Frequency, measured by plethysmography, was the major metric, and a pause defined by breathing cessation >2.5 times the average frequency. Mice were tested after 16 days of ip injections of vehicle or drug. On day 17, 4 mice in each group were tested after buspirone and the 5-HT(1A) receptor antagonist, 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinyl-benzamide (p-MPPI, 5 mg/kg). A post-hypoxic pause was present in 6/8 animals given vehicle and 1/16 animals given buspirone at either dose, but always present (8/8) with p-MPPI, regardless of buspirone dose. Post-hypoxic frequency decline was blunted by buspirone (-10% vehicle vs. -5% at both doses) and restored by p-MPPI; ventilatory stability as described by the coefficient of variation which was reduced by buspirone (p<0.04) was increased by p-MPPI (0.01). In conclusion, buspirone administration after 2 weeks acts through the 5-HT(1A) receptor to reduce post-hypoxic ventilatory instability in the B6 strain.
authors.affiliation: Department of Pulmonary, Critical Care, and Sleep Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Moore
authors.forename: S
authors.initials: S
authors.lastname: Chai
authors.forename: C B
authors.initials: CB
authors.lastname: Gillombardo
authors.forename: A
authors.initials: A
authors.lastname: Carlo
authors.forename: L M
authors.initials: LM
authors.lastname: Donovan
authors.forename: N
authors.initials: N
authors.lastname: Netzer
authors.forename: K P
authors.initials: KP
authors.lastname: Strohl
mesh_terms: D000818:Animals; D001049:Apnea / Q000188:drug therapy* / Q000209:etiology; D002065:Buspirone / Q000627:therapeutic use*; D000860:Hypoxia / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010991:Plethysmography; D012119:Respiration / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
chemical_list: D017366:Serotonin Receptor Agonists; D002065:Buspirone