Interactions between the Effects of Opioid, Serotonin and Alpha-2-Adrenergic Receptor Agonists on Growth Hormone Release in the Male Rat

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Abstract
In a previous study, we identified a number of negative interactions between the growth hormone (GH)-releasing effects of opioid, alpha 2 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 alpha 2 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.

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