Postnatal development of opioid regulation of micturition in the kitten

Endogenous opioids tonically regulate micturition in adult mammals. The present study sought to determine if opioids regulate micturition in neonatal kittens. Naloxone (up to 2 mg/kg given i.p. or i.v. to unanesthetized/ketamine-anesthetized or chloralose-anesthetized kittens, respectively), an opioid receptor antagonist, produced no effects in unanesthetized, ketamine-anesthetized, or chloralose-anesthetized kittens that had been prepared for bladder pressure recording, until 3 weeks of age. This indicates that endogenous opioids are not tonically regulating micturition in neonatal kittens. From 3 weeks up to at least 6 weeks of age, naloxone (100 micrograms/kg i.p. or i.v.) weakly facilitated bladder activity by transiently increasing the amplitude and/or duration of bladder contractions, but no effects on frequency of contractions was recorded. Morphine (up to 2 mg/kg given i.p. or i.v. to unanesthetized/ketamine-anesthetized or chloralose-anesthetized kittens, respectively), an opioid agonist, did not inhibit bladder contractions in unanesthetized or ketamine-anesthetized neonatal kittens, but it did inhibit (at a threshold dose of 100 micrograms/kg) and completely abolished (at a dose of 300 micrograms/kg) bladder activity in chloralose-anesthetized kittens in a dose-dependent, naloxone-reversible manner. Surprisingly, following morphine administration to unanesthetized or ketamine-anesthetized neonatal kittens, naloxone now produced an adult-like enhancement of bladder activity. These latter results indicate that opioid receptors, whose inhibitory effects are anesthetic-dependent, are present along the micturition reflex pathway in neonates. Immunohistochemical studies of the sacral spinal cord revealed that opioid peptides are distributed similarly in neonatal and adult cats.