Opioid receptor activation resets the hypothalamic clock generating growth hormone secretory bursts in the rat

Plasma growth hormone (GH) concentrations were measured serially every 20 min for 6 h in unrestrained chronically-catheterised male rats to define physiological GH pulsatile secretory patterns. Bursts of GH secretion lasted 69 +/- 5 min and occurred every 177 +/- 4 min. Intravenous administration of the opioid receptor agonist morphine (200 micrograms/kg) caused an immediate GH burst of normal duration (63 +/- 3 min) in all animals. This burst of secretion occurred whatever the phase of the background GH cycle and was followed by normal trough GH levels; a second GH burst occurred 177 +/- 6 min later, an inter-burst period not different from controls. Opioid receptor blockade with naloxone (5 mg/kg) administered i.v. every 20 min during spontaneous GH bursts significantly lengthened the interburst interval from 177 +/- 4 to 200 +/- 9 min (P = 0.015). Naloxone did not affect synchronisation of the GH rhythm induced by morphine but lengthened the duration of GH secretory bursts from 69 +/- 5 to 94 +/- 9 min (P = 0.017). The findings indicate that opioid receptor activation resets the hypothalamic mechanism generating pulsatile GH secretion and that both the period of the GH rhythm and duration of the GH burst is normally shortened by opioid mechanisms.