Effects of 8-OH-DPAT on respiratory rhythmical discharge activity in isolated neonatal rat brainstem slice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of 5-HT1A receptors in the generation and modulation of basic respiration rhythm.</p><p><b>METHODS</b>Brainstem slices of 20 newborn SD rats (0-3 days) were prepared and respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve was recorded by suction electrode on these preparations including the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets retained, and the effects of 5-HT1A receptors on RRDA were investigated by application of specific agonist of 5-HT1A receptors 8-OH-DPAT in the perfusion solution. The 20 neonatal rats were divided into 4 groups and the brainstem slices were perfused continuously for 10 min with different concentrations of 8-OH-DPAT (1, 5, 10, 20 micromol/L, respectively). RRDA was recorded before and 1, 3, 5 min after 8-OH-DPAT perfusion.</p><p><b>RESULTS</b>The respiratory cycles (RC) varied significantly between the different time points of 8-OH-DPAT administration (F=181.219, P<0.001), which was the shortest before 8-OH-DPAT administration and increased progressively after administration till reaching the maximum 5 min after the administration. The RC also varied significantly between different 8-OH-DPAT concentrations (F=61.675, P<0.001). At each time point after 8-OH-DPAT administration, RC was the shortest with 1 micromol/L and maximum with 20 micromol/L 8-OH-DPAT. A crossover effect was observed between the time and administered 8-OH-DPAT concentration (F=22.940, P<0.001). The integrated amplitude (IA) was significantly different between different time points of 8-OH-DPAT administration (F=20.949, P<0.001), and the application of 10 and 20 micromol/L 8-OH-DPAT resulted in significant IA decrement (F=5.050, P=0.017; F=51.389, P=0.001, respectively). Different concentrations of 8-OH-DPAT also significantly affected IA (F=41.027, P<0.001), and at each time point after administration, IA was the maximum with 1 micromol/L and minimum with 20 micromol/L 8-OH-DPAT, also showing a crossover effect between time and 8-OH-DPAT concentration (F=3.483, P=0.002).</p><p><b>CONCLUSIONS</b>8-OH-DPAT induces a dose-dependent increase in RC and a dose-dependent inhibition of the IA and burst frequency, with long-lasting inhibitory effect on the inspiration. 5-HT1A receptors play an important role in the modulation of the RRDA in isolated neonatal rat brainstem slice.</p>