Serotonin as a modulator of glutamate- and GABA-mediated neurotransmission: Implications in physiological functions and in pathology

The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a classical neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus oil the modulatory action of 5-HT oil the effects of glutamate and gamma-arnino-butyric acid (GABA), which arc the principal neurotransmitters mediating respectively excitatory and inhibitory signals ill the CNS. Examples of interaction at pre-and/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.