“…Methoxamine, a highly lipid-soluble rxiadrenoceptor agonist, increases both circulating adrenocortico trophic hormone (ACTH) and cortisol, and this effect is blocked by the specific «i-adrenoceptor antagonist, thymoxamine [1, 2], Furthermore, thymoxamine alone is able to atte nuate diurnal changes in serum cortisol [2], particularly those induced by food [3]. As these effects are not paralleled by the use of epinephrine [4] or norepinephrine [ 1 ], which do not cross the blood-brain barrier, it has been suggested that central (nor)adrenergic pathways stimulate hypothalamic corticotro phin-releasing factor or factors (CRFs) [5].There is also a substantial body of evidence in favour of in hibitory modulation of the hypothalamo-pituitary-adrenal axis by opiates, such as morphine, nalorphine, buprénorphine and codeine [6][7][8][9], and opioid peptides including |J-endorphin and the met-enkephalin analog. £)-Ala2-MePhe'-met-enkephalin-[0]-o 1 (DAMME, FK-33,824) [10][11][12][13], This inhibition can be overcome by high doses of the opiate antagonist, naloxone [7,11,12]; naloxone itself will also elevate plasma ACTH and cor tisol under basal conditions, suggesting the existence of tonic opioid inhibition of ACTH secretion [14][15][16].…”