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, 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.
Chapman
I M
IM
Department of Medicine, Flinders University, Adelaide, Australia.
Kapoor
R
R
Willoughby
J O
JO
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus; D019329:Idazoxan; D007267:Injections; D008297:Male; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D004146:Dioxanes; D004745:Enkephalins; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D011814:Quipazine; D013006:Growth Hormone; D003000:Clonidine; D019329:Idazoxan