Effects of U‐50,488H withdrawal on catecholaminergic neurones 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 analysed in the right ventricle of rats chronically treated with the κ‐agonist 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 injected with saline or naloxone (3 mg kg−1, s.c.) to precipitate a withdrawal syndrome. 3 After naloxone administration to U‐50,488H‐ treated rats we found neither behaviour signs of physical dependence nor changes 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 decreased the 3,4‐dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover. 5 Importantly and in contrast to μ‐agonists, the present results demonstrate that U‐50,488H withdrawal produced a decrease in the NA and dopamine turnover, without behavioural signs of physical dependence. British Journal of Pharmacology (1998) 124, 1060–1064; doi:10.1038/sj.bjp.0701939