THYROTROPIN-RELEASING-HORMONE STIMULATES PERINATAL RAT RESPIRATION IN-VITRO

In the present study, we test whether thyrotropin-releasing hormone (T RH) stimulates respiratory frequency in perinatal rats by acting at re gions of the medulla responsible for respiratory rhythmogenesis, the p re-Botzinger complex. We also test whether TRH stimulates respiration in the fetal rat at a time shortly after the inception of respiratory rhythmogenesis [embryonic days (E) 17-18]. Two in vitro experimental m odels were utilized: the isolated brain stem-spinal cord preparation f rom fetal (E17-E18) and neonatal [postnatal days (P) 0-2] rats and the medullary slice preparation isolated from neonatal rats (P1-P2). Bath application of TRH caused a dose-dependent, reversible increase (maxi mum increase approximate to 60%) in the frequency of respiratory rhyth mic neural discharge generated by brain stem-spinal cord [half-maximal effective concentration (EC(50)) approximate to 9 nM] and medullary s lice (EC(50) approximate to 2.5 nM) neonatal rat preparations. Pressur e injection of TRH unilaterally into the region of the pre-Botzinger c omplex of the neonatal medullary slice caused an similar to 28% increa se in the frequency of respiratory discharge. Application of TRH to th e medium bathing fetal rat brain stem-spinal cord preparations caused an approximately threefold increase in respiratory discharge frequency . We conclude that. TRH stimulates respiratory discharge frequency fro m the time near inception of respiratory motor discharge and acts dire ctly at the pre-Botzinger complex.