The Role of Serotonin in Orbitofrontal Function and Obsessive-Compulsive Disorder

Abstract

Serotonin is crucial for orbitofrontal cortex function and for the treatment of obsessive-compulsive disorder. Using a neurocomputational model of the role of serotonin in orbitofrontal function, we show that (a) low serotonin leads to perseverative neuronal activity, with the network getting “stuck” in specific states; (b) low serotonin leads to an increased tendency both to develop obsessions—strong attractors to which the network activity tends and which are difficult to escape—and to fall into existing obsessions; (c) excessive glutamatergic activity, which may occur in obsessive-compulsive disorder, also leads to an increased tendency to develop obsessions and fall into existing obsessions; (d) increasing serotonin decreases these pathological tendencies, even if they are caused by excessive glutamatergic activity; and (e) the different effects of 5-HT 1A and 5-HT 2A serotonin receptors on neuronal activity explain the differential effects of drugs that target these receptors.