Effect of melatonin treatment on 24-hour variations in hypothalamic serotonin and dopamine turnover during the preclinical phase of Freund's adjuvantarthritis in rats

The effect of melatonin treatment on time-of-day variations in hypothalamic serotonin (5-HT) and dopamine (DA) turnover was studied in rats treated wi th Freund's complete adjuvant (FCA). Animals received s.c. injections of 30 mu g of melatonin or vehicle 1 h before lights off for 11 days. On day 10 of treatment, FCA or its vehicle was s.c. injected, and 2 days later, the r ats were killed at 6 different time intervals throughout a 24-hour cycle. H ypothalamic 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA), DA and 3,4-dihydr oxyphenylacetic acid (DOPAC) levels were measured by HPLC. 5-HT and DA turn over were estimated from the 5-HIAA/5-HT and DOPAC/DA ratios, respectively. In the anterior hypothalamus, time-of-day variation in 5-HT turnover was s uppressed by FCA, an effect counteracted by melatonin treatment. Melatonin also prevented FCA effect on medial hypothalamic 5- HT turnover, while in t he posterior hypothalamus, similar daily variations of 5-HT turnover were f ound in all experimental groups. As far as DA turnover, FCA or melatonin ad ministration suppressed its daily variations in the anterior hypothalamus. Time-of-day variations in medial hypothalamic DA turnover were similar in a ll groups while only rats treated with melatonin and FCA or its vehicle exh ibited significant daily changes of DA turnover in the posterior hypothalam us. Results indicate that melatonin treatment affects partly the 24-hour pa ttern of variation of hypothalamic 5-HT and DA turnover at an early phase o f FCA arthritis in rats.