Neuroendocrine and behavioural effects of the serotonin releasers 3,4-methylenedioxymethamphetamine and fenfluramine in rats

The substituted amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine share the common neurochemical effect of releasing 5-HT from serotonergic nerve terminals. 5-HT has stimulatory effects in rodents on the hypothalamic neurons that regulate pituitary-adrenocortical function. Behavioural responses to MDMA and fenfluramine may have an important role in modulating their neuroendocrine effects, and in converse, hypothalamic-pituitary-adrenal (HPA) function may have an important role in modulating behavioural effects. The effects of acute administration of d-fenfluramine (3 and 6 mg kg^-1) and MDMA (5 and 10 mg kg^-1) were examined in a test design which allowed serial blood samples to be obtained whilst continuous home cage activity was monitored over a six hour period. At the end of the test animals were sacrificed and neurotransmitter levels in the hypothalamus and cortex were examined. The administration of MDMA and fenfluramine resulted in elevated corticosterone levels which were similar with respect to both size, time of onset and duration of response. A corresponding increase in locomotor activity was observed following MDMA treatment whereas the response to fenfluramine was weaker and of shorter duration. These data demonstrated that although both d-fenfluramine and MDMA share the common neurochemical action of acutely releasing 5-HT from serotonergic nerve terminals, they have quite different behavioural effects.