Serotonergic fuctioning in depressed stroke, nondepressed stroke, and in healthy elderly

grantor: University of TorontoBackground. Considering age-related decline in 5HT function, we examined the effect of aging, gender, and a fixed dose of 30mg of oral d-fenfluramine (d-FEN) on prolactin (PRL) and cortisol (CORT) responses in healthy elderly subjects. Method. Twenty-three healthy male and female volunteers aged 60-86 years participated in a single-blind, placebo-controlled, fixed-order, crossover-design challenge test. Baseline PRL and CORT values and the responses of these hormones to 30mg of oral d-FEN and placebo over a 4 hour period were measured on two separate sessions. Results. Compared with placebo, the net changes in PRL and CORT responses (change scores from baseline) were significantly greater following d-FEN, (drug by time, F = 18.60, df = 3.66, p = 0.001; F = 4.13, df = 3.66, p = 0.01). Peak PRL responses (maximum change from baseline following d-FEN) were relatively robust compared to CORT responses. Women had greater peak PRL concentration than men (p = 0.014). Peak PRL concentration was positively correlated with plasma nor-d-FEN concentration (p = 0.039) and negatively correlated with body weight (p = 0.037). Although the weight adjusted dose used in this study (0.44mg/Kg) was higher than the recommended therapeutic dose of d-FEN (0.2-0.3mg/Kg), the peak PRL responses were modest and only two participants experienced side effects. Within this group of elderly subjects, age had no effect on d-FEN induced PRL and CORT responses. Conclusions. d-FEN can be employed as a safe serotonergic probe in the elderly and PRL responsivity to d-FEN is a reliable index of central 5HT function in this age group. Given the modest prolactin responses, it might be desirable to employ a dose in the upper therapeutic range (45-60mg) to maximise hormonal responses to d-FEN challenge tests in the elderly.M.Sc