OPIOID DEPRESSION OF RESPIRATION IN NEONATAL RATS

1. The effects of opioid receptor agonists and antagonists on the brea thing pattern of neonatal rats were studied. Three experimental approa ches were taken. In the first approach, the effects of opioid agonists and antagonists on the spontaneous respiratory neural activity genera ted by brainstem-spinal cords isolated from neonatal rats aged 0-4 day s postnatal (P0-4) maintained in vitro were studied. Secondly, similar studies were performed utilizing medullary slice preparations consist ing of respiratory rhythm-generating regions (pre-Botzinger complex). Thirdly, whole-body plethysmographic recordings were obtained from una naesthetized neonatal (P0-18) rats before and after Is. administration of opioid-receptor agonists and antagonists. 2. The mu-receptor agoni sts morphiceptin and DAGO (Tyr-D-Ala-Gly-[NNMePhe]-Gly-ol), when added either to the solutions bathing the brainstems of neonatal rat brains tem-spinal cord preparations or bathing the medullary slice preparatio ns, resulted in a naloxone-reversible, dose-dependent decrease in the frequency of respiratory rhythmic discharge. 3. The respiratory burst frequency and amplitude in vitro were unaffected by the addition of th e delta-opioid receptor agonist DPDPE ([D-pen(2.5)]-enkephalin) and th e Ic-opioid receptor agonist U50488 s-[+]-3,4-dichloro-N-methyl-N-(2-[ -1-pyrrolidinyl] cyclohexyl)benzeneacetamide) or the opioid receptor a ntagonist naloxone. 4. Intraperitoneal administration of the mu-opioid receptor agonist fentanyl resulted in a naloxone-reversible, dose-dep endent decrease in the frequency and amplitude of breathing of unanaes thetized neonatal rats (P0-P10). I.P. administration of the delta-opio id receptor agonist DPDPE did not affect breathing of neonatal rats un til. the second week postnatally. 5. We conclude that opioids suppress the frequency of neonatal rat respiration by acting via mu-opioid rec eptors located within regions of the ventral medulla containing respir atory rhythm-generating centres (the pre-Botzinger complex). delta-Opi oid receptor activation does not affect breathing in neonatal rats unt il approximately the second week postnatally.