EFFECTS OF U-50,488H WITHDRAWAL ON CATECHOLAMINERGIC NEURONS OF THE RAT VENTRICLE

1 In the present study the changes in noradrenaline (NA) and dopamine (DA) content and turnover during naloxone-induced withdrawal were anal ysed in the right ventricle of rats chronically treated with the rc-ag onist U-50,488H. 2 Rats were rendered tolerant by administration of U- 50,488H twice a day for 4 days. On the day of death the animals were i njected with saline or naloxone (3 mg kg(-1), s.c.) to precipitate a w ithdrawal syndrome. 3 After naloxone administration to U-50.488H- trea ted rats we found neither behaviour signs of physical dependence nor c hanges in the tissue content of noradrenaline (NA). However, naloxone induced a decrease in both cardiac normetanephrine (NM) levels and NA turnover. 4 Similarly, naloxone enhanced the dopamine content and decr eased the 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dop amine turnover. 5 Importantly and in contrast to mu-agonists, the pres ent results demonstrate that U-50,488H withdrawal produced a decrease in the NA and dopamine turnover, without behavioural signs of physical dependence.