Serotonin

Serotonin

An association between serotonergic transmission and anxiety disorders was established more than 30 years ago with reports (Graeff and Schoenfeld, 1970; Geller and Blum, 1970) that inhibitors of serotonin synthesis (such as p-chlorophenylalanine) reduced the ability of punishment (e.g., footshock) to suppress operant responding. Many studies have confirmed and embellished the basic findings that destruction of serotonergic pathways and or a reduction in the synthesis of this biogenic amine results in an animal behaving as if it had been administered an anxiolytic. There is a complementary body of evidence that serotonin receptor activation exacerbates anxiety. For example, challenge doses of meta-chlorphenylpiperazine (a serotonin agonist) were anxiogenic in PD patients (Charney et al., 1987b), individuals with OCD (Zohar et al., 1987) and in patients with GAD (Nutt, 2001). The observation that anxiety can initially be exacerbated in GAD patients receiving SSRIs (Nutt, 2001) provides perhaps the most compelling evidence that acute elevation of synaptic serotonin is anxiogenic.