Studies on the pharmacology of central opioid-induced increases in plasma catecholamines in conscious rats

Centrally-administered opioid peptides produce elevations in levels of catecholamines in plasma in conscious rats. To investigate the opioid receptor involved in mediating this response, morphine (3.5-105 nmol), [D-Ala2-D-Leu5]enkephalin (DADL, 1.05-35 nmol) and U50, 488H (35-1160 nmol), relatively selective ligands for the mu, delta and kappa receptors respectively, were injected intracerebroventricularly into conscious rats and the levels of catecholamines in plasma determined at the peak of the response. Each agonist produced dose-dependent elevations in levels of noradrenaline and adrenaline, the order of potency being DADL approximately equal to morphine greater than U50,488H. These results exclude involvement of the kappa receptor but do not distinguish between an effect mediated by a mu or delta receptor. The responses to morphine were blocked in the presence of 300 nmol naloxone but were not altered by 41.5 nmol RX 781094, a selective alpha 2-adrenoceptor antagonist. The elevation in levels of adrenaline in plasma produced by small doses of the agonists was not related to behavioural changes.