Serotonin receptors: a review of their function and significance in psychiatric disease

ABSTRACT

Thirty-three years ago Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline [D] and morphine [M] to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification often serotonin receptor sub-types in rat brain. While there is some controversy over the functional importance of many of these receptor sub-types, there is evidence that they full into two major groups according to the nature of their coupling to secondary messengers or ion channels. Thus the 5HT1 and 5HT2 receptors appear to occupy the G protein receptor subfamily which may be coupled either to adenylate cyclase [most 5HT1 sub-types] or phosphatidy 1 inositol [5HT2 sub-types]. The central 'M' receptors [now tenned 5HT3] appear to occupy a ligand gated ion channel super family. The cloning of these receptor sub-types has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in thermoregulation, modulation of cardiovascular function, eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the etiology of these diseases is shown in Table 2