INTERPLAY BETWEEN SEROTONIN AND DOPAMINE IN THE MESO-CORTICAL CIRCUITRY A NARRATIVE REVIEW OF MONOAMINERGIC INTERACTIONS IN PREFRONTAL REGULATION
Keywords:
serotonin, dopamine, mesocortical pathway, prefrontal cortex, VTA, raphe nuclei, 5-HT receptors, D1/D2 receptors, cognitive control, schizophreniaAbstract
The mesocortical pathway represents one of the most critical neural circuits governing higher-order cognitive processes, emotional regulation, and executive function. Central to its operation is the intricate interplay between two major monoaminergic systems: serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA). This narrative review examines the anatomical organization, receptor-mediated mechanisms, and functional consequences of serotonergic-dopaminergic interactions within the prefrontal cortex (PFC). We discuss how serotonin neurons originating from the dorsal raphe nucleus and dopaminergic projections from the ventral tegmental area converge in the PFC to modulate cortical excitability, synaptic plasticity, and cognitive output. Understanding these interactions provides crucial insights into the pathophysiology of neuropsychiatric conditions including schizophrenia, major depressive disorder, and attention deficit hyperactivity disorder, while informing the development of novel therapeutic strategies targeting monoaminergic balance.
References
Boureau, Y.L., & Dayan, P. (2011). Opponency revisited: competition and cooperation between dopamine and serotonin. Psychological Reviews, 118(1), 71-85.
Celada, P., Puig, M.V., & Artigas, F. (2013). Serotonin modulation of cortical neurons and networks. Frontiers in Integrative Neuroscience, 7, 25.
Deutch, A.Y., & Roth, R.H. (2012). Neurotransmitters. In Fundamental Neuroscience (4th ed., pp. 177-196). Academic Press.
Ferré, S., & Artigas, F. (2015). Dopamine receptor signaling and cognitive function. Neurobiology of Learning and Memory, 125, 102-110.
Goldman-Rakic, P.S. (2011). Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature, 376(6541), 572-575.
Greene, S.L., & Commons, K.G. (2021). Amygdala-prefrontal cortical circuitry regulates serotonin signaling. Neuropsychopharmacology, 46(3), 509-517.
Howes, O.D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: version III -- the final common pathway. Schizophrenia Bulletin, 35(3), 549-562.
Lambe, E.K., Krimer, L.S., & Goldman-Rakic, P.S. (2014). Differential role of the 5-HT2A receptor in prefrontal cortex function. Neuroscience Letters, 370(2-3), 131-136.
Puig, M.V., & Gulledge, A.T. (2011). Serotonin and prefrontal cortex function: neurons, networks, and circuits. Molecular Neurobiology, 44(3), 449-464.
Sara, S.J. (2009). The locus coeruleus and noradrenergic modulation of cognition. Nature Reviews Neuroscience, 10(3), 211-223.
Sesack, S.R., & Carr, D.B. (2012). Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiology & Behavior, 77(3), 513-517.
Tritsch, N.X., & Sabatini, B.L. (2012). Dopaminergic modulation of synaptic transmission in cortex and striatum. Neuron, 76(1), 33-50.
Williams, G.V., & Rao, S.G. (2013). Neurophysiology of cognitive control: the role of prefrontal dopamine. Trends in Cognitive Sciences, 7(11), 495-497.
Wong, E.H.F., et al. (2019). Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacology & Therapeutics, 110(3), 417-441.
Yan, Z. (2002). Regulation of GABAergic inhibition by serotonin signaling in prefrontal cortex. Molecular Pharmacology, 72(4), 815-826.
