5-HT1A receptor-regulated signal transduction pathways in brain

Abstract

Serotonin is an influential monoamine neurotransmitter that signals through a number of receptors to modulate brain function. Among different serotonin receptors, the serotonin 1A (5-HT1A) receptors has been tied to a variety of physiological and pathological processes, notably in anxiety, mood, and cognition. 5-HT1A receptors couple not only to the classical inhibitory G-protein-regulated signaling pathway, but also to signaling pathways traditionally regulated by growth factors. Despite the importance of 5-HT1A receptors in brain function, little is known about how these signaling mechanisms link 5-HT1A receptors to regulation of brain physiology and behavior. Following a brief summary of the known physiological and behavioral effects of 5-HT1A receptors, this article will review the signaling pathways regulated by 5-HT1A receptors, and discuss the potential implication of these signaling pathways in 5-HT1A receptor-regulated physiological processes and behaviors.

5-Hydroxytryptamine–Mediated Neurotransmission Modulates Spontaneous and Vagal-Evoked Glutamate Release in the Nucleus of the Solitary Tract Effect of Uptake Blockade

“…That is, although 5-HT uptake is blocked immediately, the activation of 5-HT 1A receptors causes an initial reduction in the overall release of 5-HT in the cortex until the 5-HT 1A receptor desensitizes (Artigas et al, 1996). However, there is no evidence that in the NTS 5-HT 1A receptors are acting, as they do in the dorsal raphe as somatodendritic autoreceptors, so these NTS 5-HT 1A receptors should be considered to be postsynaptic (heteroreceptors), that is, on terminals other than those of raphe projections, presumably similar to those that have been well described in the hippocampus (Riad et al, 2000;Polter and Li, 2010). Furthermore, the present observation that activation of 5-HT 1A receptors failed to decrease the amplitude of the mEPSC indicates that these receptors are located presynaptic to the recorded NTS neurons.…”

Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer’s disease: A post-mortem study with PET radiopharmaceuticals

“…More recently, increased hippocampal activation in MCI has also been hypothesized to be a dysfunctional condition instead of a beneficial functional compensation (Bakker et al, 2012;Tahmasian et al, 2015). Indeed, 5-HT 1A receptors are coupled to Gi/o proteins for signal transduction, and their activation in hippocampus results in adenylyl cyclase inhibition and GIRK activation which strongly inhibits the neuronal firing and excitability (Polter and Li, 2010). An early loss of 5-HT 1A receptors functionality could therefore indirectly contribute to a greater and potentially harmful hippocampal activity.…”

Association of 5-HT1A Receptors with Affective Disorders

“…The third coupling is with the 5-HT 1A auto-receptors and, to a lesser extent, 5-HT 1B and 5-HT 1D . This causes inhibition of the opening of Ca 2+ channels from the presynaptic neuron, which then inhibits the release of 5-HT into the synaptic cleft, thus regulating the intensity and duration of the nerve impulse from the presynaptic neuron (i.e., negative feedback or self-inhibition), mainly in neurons of the raphe, exerting the end the signaling of the presynaptic neurons and the resumption of the release of 5-HT neurons from the raphe to the postsynaptic neurons through the limbic areas [100]. In this context, chronic administration of SSRIs induces internalization of the 5-HT 1A auto-receptors and the neurons of the raphe [101], since the increase in the availability of 5-HT in the cleft overstimulates those auto-receptors while also desensitizing and internalizing them.…”

“…This process is associated with the phosphorylation of the carboxylic chain Figure 2. Model of the transduction pathways that may be activated by the 5-HT 1A -R; modified according to Polter and Li [100]. and the third intracellular loop of the receptor.…”