Serotonin/serotonergic system receptors

Serotonergic systems are also affected by adolescent treatment in a sexually dimorphic manner. During adolescence, at doses that produce plasma nicotine doses similar to levels found in smokers, nicotine decreases serotonin receptors specifically in the cortex, in female rats. However, in the midbrain, there was an increase in males (Xu et al. 2002). 

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. 

Some evidence indicates that other drugs with action on the serotonergic system may be associated with efficacy in OCD. Tryptophan, a precursor of serotonin, was shown in a small placebo-controlled study to have an effect size similar to that of the SSRls (S. A. Montgomery et al. 1992). Mianserin, which has 5-HTjq and 5-HT2C receptor affinities, has also been reported in a small placebo-controlled study to be more effective than placebo. This last result raises the possibility that 5-HTjp or 5-HT2C may be the more specific receptors for OCD. The provocation of obsessional symptoms by m-chloro-phenylpiperazine (mCPP), which also has affinities for 5-HT,p and 5-HT2C, reinforces this concept (Zohar et al. 1988a). 

Vetulani J, Lebrecht V, Pile A. Enhancement of responsiveness of the central serotonergic system and serotonin-2 receptor density in rat frontal cortex by electroconvulsive treatment. EurJ Pharmacol 1981 76 81. 

A snoRNA HBII-52 is located in the defective region of PWS. HBH-52 binds to an ESS in exon Vb of HTR2C encoding the serotonin receptor 2C, and its disruption in PWS causes aberrant splicing of HTR2C and potentially accounts for dysfunctional serotonergic system in PWS (Kishore and Stamm, 2006). 

Several psychological disorders are currently being discussed in terms of the effect of the physical state of the membrane lipids on neurotransmitter receptor function. Hibbeln and Salem (1995) suggest that serotonin levels and membrane 22 6n-3 content are directly linked, whereby low 22 6n-3 yields low serotonin. This results in an individual being susceptible to depression or other affective diseases. These authors suggest that the depletion of 22 6n-3 induces a change in membrane physical properties, which, in turn, influences the function of either serotonergic receptors or serotonin reuptake systems. 

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