Functional interrelationships between adrenergic and opioid systems in the neuroregulation of growth hormone secretion in infant rats

Functional interrelationships between hypothalamic adrenergic and opioid systems were studied in 10-day-old male and female rats. Either clonidine (150-mu-g/kg, sc), an alpha-2-adrenoceptor agonist, or FK 33-824 (1 mg/kg, sc), a synthetic analog of met-enkephalin, increased plasma growth hormone (GH) levels, the increment being significantly higher with FK33-824 than with clonidine. Pharmacologic blockade of opioid receptors with naloxone (5 mg/kg, sc) did not modify either basal GH levels, or the GH response to clonidine, whereas blockade of alpha-2-adrenoceptors with yohimbine (2.5 mg/kg, sc) reduced basal GH levels and partially counteracted the FK 33-824-induced GH rise, Clonidine (150-mu-g/kg, sc, twice daily) administered from postnatal day 5 to 9, increased basal GH levels and pituitary GH content. In these pups, acute administration of clonidine failed to further release GH, but the GH response to acute administration of FK 33-824 was significantly enhanced. A 5-day treatment with FK 33-824 (1 mg/kg, sc, twice daily), neither modified basal GH levels, nor pituitary GH content Under these conditions, the in vivo GH response to an FK 33-824 challenge was significantly enhanced, and the response to clonidine was preserved. Pituitaries from FK 33-824-pretreated rats were hyperresponsive to GH-releasing hormone (10(-7) M). In summary, our data indicate that in rat pups: 1) two separate components i.e. one adrenergic, the other extra-adrenergic, subserve the GH-releasing effect of opioid peptides; 2) in contrast to short-term stimulation of alpha-2-adrenoceptors, stimulation of opioid receptors does not trigger GH synthesis or induce down-regulation or tolerance; 3) short-term opioid stimulation does not affect an alpha-2-adrenergic challenge, but sensitizes to an opioid challenge.