5-HT-related drugs and human experimental anxiety

Clinical observations and double-blind studies demonstrated an anxiolytic effect of drugs that facilitate serotonergic transmission on several anxiety disorders. There is a latency of several weeks for their anxiolytic effect to take place. There may be, in addition, a biphasic effect, i.e., an acute anxiogenic effect followed by an anxiolytic effect after chronic use. In addition, acute administration of m-chlorophenylpiperazine (MCPP), an agonist of 5-HT-1 receptors, increased anxiety in normal volunteers as well as in patients with panic or obsessive-compulsive disorders. Studies in health volunteers have been performed in our laboratory to explore the acute effect on human anxiety of drugs that selectively influence 5-HT neurotransmission. We observed that acute administration of chlorimipramine enhanced the rise in anxiety induced in healthy volunteers by speaking in front of a video camera. With a similar experimental design, we also demonstrated an anxiogenic effect of metergoline, a nonselective 5-HT receptor blocker. It is suggested that the proanxiogenic effect of acute administration of 5-HT uptake inhibitors may be due to impaired 5-HT neurotransmission.