Effect of d-fenfluramine on human experimental anxiety

To investigate the role of 5-HT in human anxiety, the 5-HT releaser and uptake blocker d-fenfluramine (FEN) was administered to healthy volunteers under two models of experimental anxiety. The first was a simulated public speaking (SPS) test consisting of talking in front of a video camera, anxiety being evaluated mainly by self-rating scales. The second was a conditioned fear test, in which the changes in skin electrical conductance caused by a tone associated once with an aversive white noise were measured. The doses of 15 and 30 mg FEN, PO, decreased anxiety induced by SPS in a dose-dependent way, as indicated by the anxiety factor of Norris Visual Analogue Mood Scale. In the conditioned fear test, however, the amplitude and level of skin conductance responses to the conditioned aversive stimulus were not significantly changed by FEN. The differential effects of FEN in these human experimental models of anxiety, together with similar results reported in rats, support the view that 5-HT exerts a dual action on brain mechanisms regulating anxiety, facilitating conditioned while inhibiting unconditioned fear. The presumed reduction in unconditioned fear caused by FEN may have implications for the treatment of panic disorder.