Facilitation of respiratory rhythm by a mu-opioid agonist in newborn rat pons-medulla-spinal cord preparations

We investigated the effect of a mu-opioid agonist, DAGO, on the respiratory frequency of pons-medulla-spinal cord preparations from newborn rats. Bath application of a low concentration of DAGO (0.2 microM) facilitated respiratory rhythm in pons-medulla-spinal cord preparations, whereas it induced respiratory depression in medulla-spinal cord preparations (without pons). At a higher concentration (1.0 microM), at which the inspiratory burst generation in the medulla was strongly depressed, the respiratory rhythm in half of the pons-medulla-spinal cord preparations increased and then decreased, thus showing a biphasic response. In the other half of these preparations, only the facilitatory effect was observed. The burst rate of pre-inspiratory neurons in the rostral ventrolateral medulla was also facilitated by DAGO application. Such facilitation of the respiratory rhythm is probably due to disinhibition of a pontine inhibitory system. Our findings also suggest the existence of a pontine excitatory system, which is depressed by the pontine inhibitory system under control conditions.