Abnormal ACTH and prolactin responses to fenfluramine in rats exposed to single and multiple doses of MDMA

Abstract

The present study examined the persistent functional consequences associated with exposure to single and multiple doses of (±) 3,4-methylenedioxymethamphetamine (MDMA) as reflected by the neuroendocrine responses to d,l-fenfluramine (FEN). Adult male rats were administered a single dose of MDMA (20 mg/kg, SC) and challenged 2 weeks later with saline or FEN (2, 4, 6 and 8 mg/kg, SC). The corticotropin (ACTH) response to FEN (6 and 8 mg/kg) was blunted and the prolactin response to FEN (4 and 6 mg/kg) was enhanced in MDMA pre-treated rats. The ACTH and prolactin responses to FEN (6 mg/kg, SC) were then evaluated 4, 8 and 12 months after exposure to single and multiple doses MDMA (20 mg/kg, SC and 20 mg/kg, SC, bid, × 4 days, respectively). The ACTH response to FEN was significantly reduced at 4 and 8 months in both MDMA treatment groups, and at 12 months in the multiple dose group only. In contrast, the prolactin response to FEN was enhanced in both groups of MDMA treated rats at 4 months, but only in the multiple dose group at 8 months. By 12 months, the prolactin response to FEN had normalized. Following multiple doses of MDMA, 5-HT concentrations were reduced significantly in the frontal cortex at 4 and 12 months. The results indicate that exposure to single or multiple doses of MDMA can produce functional alterations which can persist for months, whereas the biochemical sequelae were less robust and shorter lived.