engleski

Dose‐dependent depression of preBotzinger Complex (pBC) region neurons by local application of the 5HT1A receptor agonist 8OH‐DPAT

IV administration of 8OH-DPAT increases breathing rate and has been used to counteract opioid- induced depression. The mechanism by which 8OH- DPAT produces its effect is unclear. This study determined the dose-dependent effects of 8OH-DPAT on single pBC neurons. Multi-barrel micropipettes were used to record pBC neuronal activity and picoeject 8OH-DPAT (1, 10, & 100 microM) in decerebrate, vagotomized, paralyzed and ventilated dogs during isocapnic hyperoxia. Picoejection of artificial CSF had no effect on peak and time- averaged discharge frequencies (Fn), while 1 microM 8OH-DPAT depressed peak and average Fn of I neurons by ~36% but had no effect on E neurons. Both I and E neurons were similarly depressed at 10 and 100 microM, with a maximum depression of ~42 % at 100 microM. Unilateral 8OH-DPAT (200 microM, 100 nl) microinjections in 1 mm increments from the obex to 7mm rostral within the ventral respiratory column had no effect on the phrenic neurogram (PNG), while IV 8OH-DPAT (~20 mcg/kg iv) decreased TI and TE to 67.1±4.5% and 62.3±7.2%, respectively with no change in peak PNG. These data suggest that pBC region 5HT1A receptors may not be responsive to the nanoM concentrations achieved with IV administration. Therefore exogenous biogenic amines may produce their effects on the breathing pattern at locations outside the VRC and pBC in dogs. Supported by VA Med. Res. and NIH GM059234 funds.

8OH-DPAT ; pBC neurons ; dose-dependent

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