In brain stem respiratory network of mouse, GABA_B-receptor play a crucial role in rhythmic modulation. In adult animals, activation of GABA_B-receptors causes inhibition of adenylate cyclase via G_ai subunites and liberation of G_b[gamma]subunites, leading to modulation of LVA- and HVA Ca²⁺-currents as well as K⁺-currents. So far little is known about postnatal maturation of GABA_B-signaling. In the present study, the effect of GABA_B-receptor-mediated modulation of Ca²⁺-currents and the involving intracellular signaling pathway was investigated in brain stem slices of neonatal mice (P0-P15) using a combined electrophysiological, biochemical and immunohistochemical approach. In neurons of pre-Bötzinger-complex, activation of GABA_B-receptor enhanced the low voltage activated Ca²⁺ currents (LVA) in P0-P3 mice, while it decreased the LVA-Ca²⁺ currents later (P7-P15). During the same postnatal stage the expression of different G_i/o- and G_s-protein subtypes altered in brain stem respiratory network. In addition coupling of GABA_Brecepor to G_i/o and G_s, and GABA_B-recepor-mediated modulation of intracellular cAMP-level changed markedly coinciding with the changing effect of GABA_B-receptors. Our results suggest that changes of GABA_B-receptor-mediated cellular effect are accompanied by changes in involving second-messenger pathways in brain stem respiratory network of neonatal mouse. (supported by CMPB Göttingen)