The opioid m- and dopamine D ₁-receptors belong to the large family of metabotropic receptors coupled to G_i- and G_s-mediated signal pathway. It has been shown that both receptors play functional roles in central respiratory rhythm modulation. In the present study, we investigated the mutual modulation of colocalized D₁- and m-receptors during early postnatal development in the respiratory network of mouse. Activation of m-receptor by its agonist reduced the frequency of spontaneous and miniture inhibitory postsynaptic currents (sIPSCs; mIPSCs). Additional application of D₁-receptor agonist antagonized the effect of m-receptor. On the other hand, the frequency increases of both sIPSCs and mIPSCs evoked by D₁-receptor agonist could be compensated by application of m-receptor agonist. Both agonists showed no effect on amplitude of mIPSCs indicating the presynaptic nature of their action. Furthermore, both m- and D ₁-receptor mediated effects on synaptic transmission were abolished in presence of the protein kinase A (PKA) inhibitor Rp-cAMP. Thus our data demonstrated that activation of co-localized m- and D₁-receptors causes the activation of G_i-and G_s -mediated PKA-dependent signaling. Our results thus support the hypothesis that D₁-receptor plays an important role in modulation of m-opioid receptors, which might be therapeutically useful for the treatment of opioid-mediated disturbances of respiration.