Serotonin receptor function

Bankson, M.G. and Cunningham, K.A., 3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions, J. Pharmacol. Exp. Ther. 297(3), 846-852, 2001. 

Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, et al. 1999. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 397 (6717) 359. 

Blier P, de Montigny C (1998) Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 44 313-323 Bonasera SJ, Tecott LH (2000) Mouse models of serotonin receptor function toward agenetic dissection of serotonin systems. Pharmacol Ther 88 133-142 Bonhoeffer T (1996) Neurotrophins and activity-dependent development of the neocortex. Curr Opin Nemobiol 6 119-126... 

O Classic views as to the cause of major depressive disorder focus on the monoamine neurotransmitters norepinephrine (NE), serotonin (5-HT), and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning. 

Wolf, W. A. Schutz, L. J. (1997). The serotonin 5-HT2c receptor is a prominent serotonin receptor in basal ganglia evidence from functional studies on serotonin-mediated phosphoinositide hydrolysis. J. Neurochem. 69, 1449-58. 

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

Kroeze, W. K Kristiansen, K and Roth, B. L. (2002) Molecular biology of serotonin receptors structure and function at the molecular level. Curr. Top. Med. Chem. 2, 507-528. 

To date, at least four major subtypes of serotonin receptor have been described in detail and a major advance has been made with the isolation of genomic clones for these receptor subtypes. We now await the further development of selective ligands for all the serotonin receptor subtypes which may ultimately lead to a better understanding of the functional significance and clinical relevance of serotonin receptors in health and disease. Hopefully such a development will also result in the availability of more effective drugs to treat neurological and psychiatric diseases. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Strobel A, Gutknecht L, Zheng Y, Reif A, Brocke B, Lesch KP (2003) Allelic variation of serotonin receptor 1A function is associated with anxiety- and depression-related traits. J Neural Transm 110 1445-1453... 

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