CHANGES IN RIGHT ATRIAL CATECHOLAMINE CONTENT IN NATIVE RATS AND AFTER NALOXONE-INDUCED WITHDRAWAL

In this study, we determined if changes in heart catecholamine content during naloxone-induced withdrawal correlated with modifications in h eart rate. In addition, we determined plasma concentrations of cortico sterone as an index of the hypothalamo-pituitary-adrenal (HPA) axis. T he effects of naloxone on norepinephrine, epinephrine or dopamine cont ent and turnover, plasma concentrations of corticosterone and the mech anical response of the right atria of the rat were studied. Male rats were implanted with placebo or morphine pellets for 7 days. On the day of sacrifice, animals were injected with saline or naloxone 1 mg kg(- 1) s.c. to precipitate a withdrawal syndrome. Administration of naloxo ne to morphine-treated (tolerant) animals induced a decrease in atrial content of norepinephrine, epinephrine and dopamine (290.2 (11.9) ng g(-1), 15.6 (2.1) ng g(-1) and 9.52 (0.5) ng g(-1), respectively) and an increase (1.38 (0.2) ng g(-1) in the dihydroxy phenyl acetic acid/d opamine (DOPAC/DA) ratio. Administration of naloxone to morphine-treat ed animals enhanced plasma concentrations of corticosterone (435.8 (27 .6) ng ml(-1)). In the isolated right atria, L-naloxone induced an inc rease in atrial rate in preparations from morphine-treated rats wherea s in placebo-pelleted (naive) rats, L-naloxone induced a decrease. In contrast, administration of D-naloxone (inactive isomer) produced a de crease in atrial rate in preparations from placebo or morphine-treated rats. We conclude that this study has provided evidence that naloxone -induced withdrawal was characterized by activation of catecholaminerg ic neurones in the heart that was accompanied by an increase in atrial rate.