The central serotonin2B receptor as a new pharmacological target for the treatment of dopamine-related neuropsychiatric disorders: Rationale and current status of research

Abstract

The serotonin_2B receptor (5-HT_2BR), which was first cloned and characterized in the rat stomach fundus, is the most recent addition to the 5-HT₂R family. While its involvement in the regulation of gastrointestinal, vascular, pulmonary and cardiac physiology has been widely investigated, its functional role within the central nervous system (CNS) has received much less attention. Nevertheless, when considering the data available in the literature with regards to the regulatory control exerted by the central 5-HT_2BR on dopamine (DA) and serotonin (5-HT) neuron activity, a very interesting picture emerges and highlights the key role of these receptors for future therapeutic strategies of DA-related neuropsychiatric disorders. Thus, the present review, by compiling molecular, biochemical, electrophysiological and behavioral findings from the literature of the past twenty years, aims at providing a sound analysis of the current knowledge supporting the interest of the central 5-HT_2BR for future therapeutic avenues. First, we recall the neuroanatomical and functional data supporting the therapeutic relevance of the 5-HT/DA interaction in the CNS. Thereafter, after a short overview of the central expression and molecular properties of the 5-HT_2BR, as well as of the 5-HT_2BR agonists and antagonists available in the market, we will focus on the functional role of this receptor in the control of 5-HT, DA and neuroglia activity in the rodent brain. Finally, the therapeutic potential of 5-HT_2BR antagonists for improved treatment of schizophrenia and drug addiction will be discussed.

Keywords: Central serotonin(2B) receptor; Dopamine activity; Drug addiction; Schizophrenia; Serotonin activity.