Respiratory Physiology & Neurobiology 2012-07-31

Two weeks of buspirone protects against posthypoxic ventilatory pauses in the C57BL/6J mouse strain

M.W. Moore, S. Chai, C.B. Gillombardo, A. Carlo, L.M. Donovan, N. Netzer, K.P. Strohl

Index: Respir. Physiol. Neurobiol. 183(1) , 35-40, (2012)

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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 (1.5mg/kg, n=8), and high-dose buspirone (5.0mg/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-HT1A receptor antagonist, 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinyl-benzamide (p-MPPI, 5mg/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-HT1A receptor to reduce post-hypoxic ventilatory instability in the B6 strain.