Serotonin/dopamine interaction: Electrophysiological and neurochemical evidence

The interaction between serotonin (5-HT) and dopamine (DA) in the central nervous system (CNS) plays an important role in the adaptive properties of living animals to their environment. These are two modulatory, divergent systems shaping and regulating in a widespread manner the activity of neurobiological networks and their interaction. The concept of one interaction linking these two systems is rather elusive when looking at the mechanisms triggered by these two systems across the CNS. The great variety of their interacting mechanisms is in part due to the diversity of their neuronal origin, the density of their fibers in a given CNS region, the distinct expression of their numerous receptors in the CNS, the heterogeneity of their intracellular signaling pathway that depend on the cellular type expressing their receptors, and the state of activity of neurobiological networks, conditioning the outcome of their mutual influences. Thus, originally conceptualized as inhibition of 5-HT on DA neuron activity and DA neurotransmission, this interaction is nowadays considered as a multifaceted, mutual influence of these two systems in the regulation of CNS functions. These new ways of understanding this interaction are of utmost importance to envision the consequences of their dysfunctions underlined in several CNS diseases. It is also essential to conceive the mechanism of action of psychotropic drugs directly acting on their function including antipsychotic, antidepressant, antiparkinsonian, and drug of abuse together with the development of therapeutic strategies of Alzheimer's diseases, epilepsy, obsessional compulsive disorders. The 5-HT/DA interaction has a long history from the serendipitous discovery of antidepressants and antipsychotics to the future, rationalized treatments of CNS disorders.