Acute melatonin and para-chloroamphetamine interactions on pineal, brain and serum serotonin levels as well as stress hormone levels

para-Chloroamphetamine, an amphetamine analog, alters serotonergic neuroche mistry. In previous reports, melatonin (MEL), when administered with other amphetamine analogs, altered the decline in serotonin content produced by t hese analogs. The present studies assessed the effects of various doses of melatonin and p-chloroamphetamine on serotonin levels in numerous brain reg ions in male rats. Melatonin (10, 25 or 50 mg/kg, s.c.) and p-chloroampheta mine (3 or 5 mg/kg, s.c.) were administered and, 3 h later, brain samples a nd serum were collected. Serotonin levels in the serum and various regions of the brain were assayed using high-performance liquid chromatography. Mel atonin in combination with a high dose of p-chloroamphetamine (5 mg/kg) pro duced cumulative deficits in serotonin levels in the serum. However, seroto nin levels in the pineal, cortex or brain stem in all combined melatonin an d p-chloroamphetamine groups were not significantly different from groups t hat received p-chloroamphetamine alone. Serum adrenocorticotropin (ACTH) an d corticosterone levels were significantly elevated in the melatonin and p- chloroamphetamine combined groups, suggesting that animals receiving both t reatments were more stressed than control animals or animals receiving mela tonin or p-chloroamphetamine alone. These results indicate that melatonin d oes not alter p-chloroamphetamine-induced deficits in central serotonin lev els. The increased serum adrenocorticotropic, hormone, corticosterone and s erotonin levels observed following melatonin and p-chloroamphetamine treatm ent suggest that this combination may have adverse peripheral effects. (C) 2001 Elsevier Science B.V. All rights reserved.