Mu- vs. delta-opioid influence on respiratory and sleep behavior during development

The role of mu- vs. delta-opioid receptors in modulating cardiorespiratory and sleep/wake behavior was studied in sixteen 4- to 11-, and 26- to 33-day-old chronically instrumented piglets. Each underwent 1.5-h recordings of sleep/wake state, diaphragmatic and posterior cricoarytenoid electromyogram (EMGdi, EMGpca), heart rate, and arterial pressure, pH, and gas tensions, before and after either naltrexone (2 mg/kg i.v.), a predominantly mu antagonist, or naltrindole (4 mg/kg i.v.), a specific delta antagonist. In younger piglets, 1) naltrindole, but not naltrexone, decreased percent of time spent in active and quite sleep and increased that in wakefulness, and 2) naltrexone, but not naltrindole, increased respiratory frequency, decreased the duration of EMGdi and EMGpca activity, and increased initial summed EMGdi activity, all independently of state. Older piglets exhibited 1) increased arousal with both drugs and 2) weaker stimulation of respiratory timing and no stimulation of EMGdi or EMGpca with naltrexone and enhanced EMGpca activity with naltrindole during transitional sleep only. Thus, in early neonatal life, delta-opioid systems modulate sleep/wake behavior, whereas mu systems modulate respiration. With age, these influences change and become less specific.