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Projections stemming from the Median Raphe Nucleus (MnR) modulate dopaminergic activity within the forebrain. Additionally MnR projections are part of a behavioral dis-inhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder.

Pezzato, F.A., Can, A., Hoshino, K. et al. Psychopharmacology (2015) 232: 1441. https://doi.org/10.1007/s00213-014-3775-z

Median Raphe Nucleus (MnR) is one of two nuclei, the other being the dorsal raphe nucleus (DnR), in the midbrain-pons. The median Raphe Nucleus contains 5-hydroxytryptamine (serotonin, 5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain limbic areas that control emotional behavior. Distinct projection areas of the MnR innervates the medial septum, cingulate and dorsal hippocampus. MnR fibers are course and large with spherical varicosities. Neurotoxic 5-HT-releasing agents selectively destroy Dorsal Raphe Nucleus projection fibers without affecting the dense coarse fibers from the Median Raphe Nucleus.

Beck SG, Pan YZ, Akanwa AC, Kirby LG (2004) Median and dorsal raphe neurons are not electrophysiologically identical. J Neurophysiol 91:994–1005

The use of microdialysis and voltammetry in studies has indicated that neurotransmitter-mediated responses may be different, and chronic treatment with agonists may differentially regulate the MnR and DnR. Results from these studies have demonstrated  the selective vulnerability of MnR or DnR

Kreiss DS, Lucki I. Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei. Synapse. 1997;25:107–116.

Despite advances in understanding anxiety, the functional role of serotonergic projections from the median raphe nucleus to the dorsal hippocampus is not understood. However recently Hokkaido University examined this functional role by using the contextual fear conditioning (CFC) model of anxiety. This study was able to reduce freezing in CFC without affecting general motor activity dose-dependently by intra-MRN microinjection of mirtazapine. Mirtazapine is a noradrenergic and specific serotonergic antidepressant and through its sue suggests an anxiolytic-like effect in CFC. Intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the dorsal hippocampus. These two results suggest that the activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC.

An, Y., Inoue, T., Kitaichi, Y., Izumi, T., Nakagawa, S., Song, N., Chen, C., Li, X, Koyama, T., Kusumi, I., 2013. Anxiolytic-like effect of mirtazapine mediates its effect in the median raphe nucleus. Eur. J. Pharmacol. 720 (1-3), 192-197.