5-HT_1A Receptor: Role in the Regulation of Different Types of Behavior

Abstract—Serotonin, a brain neurotransmitter, acting via 14 types of serotonin (5-HT) receptors regulates different forms of both normal and pathological behavior. All 5-HT receptors (except for 5-HT₃ representing an ion channel (ionotropic receptor)) belong to a superfamily of metabotropic receptors coupled with G-proteins. Each receptoris characterized by a unique gene, spectrum of affinity to different agonists and antagonists, specific distribution in the brain, and a set of controlled functions. Among this diversity of 5-HT receptors, the evolutionarily most ancient 5-HT_1A receptor is of a special interest since it plays a key role in autoregulating of the brain 5-HT system. This role of 5-HT_1A receptors is caused by the peculiarities of their localization (pre- or postsynaptically on 5-HT neurons), depending on which they can exert the opposite effect on the functional activity of the 5-HT system. The review is devoted to the data of the literature and the results obtained by the authors about the factors regulating the expression and functional activity of 5-HT_1A receptors and their influence on behavior. The structure of the 5-HT_1A receptor gene was described; and the latest data on the posttranslational regulation of the activity of 5-HT_1A receptors and interaction of 5-HT receptors were given. Special attention was paid to the role of the 5-HT_1A receptor’s heterodimerization with the 5-HT₇ serotonin receptor and the functional inactivation of the 5-HT_1A receptor. The involvement of 5-HT_1A receptors in regulation of aggressive behavior, catalepsy, anxiety, depression, and unique natural adaptation (hibernation) was demonstrated. Special attention was paid to the involvement of these receptors in regulation of (1)—fear-induced defensive aggression the base of thedomestication process; (2) intermale aggression resulting in the establishment of a dominant–subordinant relationship in the animal community and underlying human asocial behavior; and (3) the mechanisms of depression and the effect of clinically efficient antidepressants of the serotonin reuptake inhibitors group . The role of 5-HT_1A/5-HT₇ heterodimerization in the mechanism of the antidepressants effect was hypothesized.