INTERACTIONS BETWEEN THE EFFECTS OF OPIOID, SEROTONIN AND ALPHA-2-ADRENERGIC RECEPTOR AGONISTS ON GROWTH-HORMONE RELEASE IN THE MALE-RAT - INTRAHYPOTHALAMIC ADMINISTRATION

In a previous study, we identified a number of negative interactions between the growth hormone (GH)-releasing effects of opioid, alpha2 and serotonin agonists when given intravenously together to male rats. To further characterise these interactions, conscious male rats were given unilateral intrahypothalamic injections of clonidine, the serotonin agonist quipazine and a mu opioid agonist (DAGO), and plasma GH levels were measured. Injection of all three drugs separately into the mediobasal hypothalamus (MBH) increased GH release. Combinations of DAGO-clonidine (p = 0.04), clonidine-quipazine (p = 0.04) and DAGO-clonidine-quipazine (p = 0.04) produced significantly less than additive GH release, whereas DAGO-quipazine produced additive release. MBH injection of the alpha2 antagonist idazoxan 10 nmol prevented the GH rise due to clonidine, but did not inhibit release due to DAGO. Injection of DAGO and clonidine but not quipazine into the preoptic-anterior hypothalamic area (PO/AHA) increased GH release, and combination injections of DAGO and clonidine produced additive release. PO/AHA idazoxan 10 nmol prevented GH release caused by both clonidine and DAGO, suggesting that idazoxan prevents opioid-induced as well as clonidine-induced suppression of somatostatin release. The inability of MBH idazoxan to block DAGO-induced GH release suggests that opioid-adrenergic interactions here are not due to an opioid GH-releasing action exerted through catecholaminergic pathways. The negative interaction previously identified between intravenous opioids and quipazine probably occurs outside the hypothalamus.