Diminished Serotonin-Mediated Prolactin Responses in Nondepressed Stroke Patients Compared With Healthy Normal Subjects

BACKGROUND AND PURPOSE: The purpose of this study was to use hormonal responsiveness to d-fenfluramine (d-FEN) challenge as a measure of central serotonin (5-HT) function in a comparative evaluation of serotonergic abnormalities between stroke patients and healthy elderly normal subjects to test the hypothesis that stroke may be associated with diminished serotonergic functioning. METHODS: Eight nondepressed medically stable stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, fixed-order, crossover design challenge test with 30 mg of oral d-FEN. Baseline prolactin (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were measured at hourly intervals over a 4-hour period. Cardiovascular responses (pulse and blood pressure) and behavioral responses were also recorded at the same time points. RESULTS: The 2 groups were comparable in demographics, body weight, plasma drug concentration, and behavioral and CORT responses. A 3-way ANOVA for repeated measures showed group differences for baseline adjusted PRL responses (change of scores from baseline). Peak PRL responses (maximal PRL change from baseline scores after treatment with d-FEN) in nondepressed stroke patients were attenuated compared with healthy elderly subjects, suggesting diminished serotonergic responsiveness in stroke patients. CONCLUSIONS: The demonstrated serotonergic hypofunctioning poststroke may contribute to the high incidence of depressive disorders in stroke patients. Serotonergic agents may have a role in augmentation of stroke recovery.