However, contemporary neuroimaging technologies mentioned above (especially functional and pharmacological MRI, and PET) combined with behavioral approaches, offer a variety of new opportunities for the investigation of the limbic system in the living human brain.134,149,158,159 Thus, recent articles report the exploration of the corticolimbic circuitries in relation to emotion and cognition.158,160,161 Multimodal in vivo imaging studies add new information on the medial prefrontal cortex and amygdala coupling,160 providing an advanced knowledge on the brain mechanism of certain pathophysiological effects of social anxiety disorder.134
As described above, 5-HT neurons send axons and terminals Inhibitors,research,lifescience,medical throughout the entire brain and therefore can potentially interact with almost all the other neuronal systems via the diversity of 5-HT heteroceptors (ie, receptors expressed by neurons that do not synthesize 5HT).100 Recent Inhibitors,research,lifescience,medical investigations in mice indicate that other mechanisms could also contribute to the 5-HT signaling. Inhibitors,research,lifescience,medical Thus, it was demonstrated that local infusion of fluoxetine (a SSRI) in the dorsal raphe nucleus stimulates the secretion of the protein S100-beta by 5-HT neurons projecting to the locus cereuleus. This protein downregulates the microRNA miR-16
in noradrenergic neurons which in turn switch on serotonergic functions.90 Reciprocally, classical neurotransmitters, especially GABAergic, catecholaminergic, glutamatergic, cholinergic, and histaminergic systems, influence the serotonergic neurotransmission at different sites, including the raphe nuclei. It is well
known that the raphe nuclei contain collections of non-5-HT Inhibitors,research,lifescience,medical neuronal elements (eg, GABAergic, glutamatergic, cholinergic, histaminergic, dopaminergic, noradrenergic) interacting with 5-HT cell bodies via their respective receptor subsets.162,163 Moreover, the richness in heteroreceptors Inhibitors,research,lifescience,medical (eg, alpha2-adrenoceptors, glutamatergic, histaminergic receptors) expressed by 5-HT terminals and other local mechanisms (eg, vesicular-filling synergy) mentioned above illustrate the extent of the reciprocal chemocommunication between serotonergic circuitries and other neurotransmitter networks. almost Other interactions of clinical importance concern the interaction between serotonergic neurotransmission and neuropeptidergic systems. It is well known that 5-HT influences the activity of the hypothalamo-pituitary-adrenal axis at multiple levels, playing a role in stress-related disorders. Thus, 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor agonists enhance CRH and ACTH secretion and, consecutively, cortisol and other hormone levels in the find more plasma.164,165 In turn, corticosteroids attenuate the activity of 5-HT1 A receptors in the dorsal raphe nucleus, the hippocampal formation and the frontal cortex.