Interplay between Serotonin 5‐HT_1A and 5‐HT₇ Receptors in Depressive Disorders

Abstract

Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety.

5-HT1A receptor gene silencers Freud-1 and Freud-2 are differently expressed in the brain of rats with genetically determined high level of fear-induced aggression or its absence

“…At the same time, the majority of 5-HT 1A receptors in this brain structure are localized presynaptically. Taking into account the crucial role of presynaptic 5-HT 1A receptors in the suppression of the brain 5-HT system functional activity [3,4,11] together with the data on antiaggressive effects of 5-HT [29] obtained data allow to suggest that decreased 5-HT 1A receptor protein level in the midbrain of highly aggressive rats could reflect a compensatory changes directed to enhancement of the brain serotonin system functioning and, hence, to reduction of excessive fear-induced aggression in rats of 85th generation of selective breeding. This suggestion is confirmed by increase of postsynaptic 5-HT 1A receptor in the hippocampus of highly aggressive rats.…”

“…Recent studies provided new evidences that being a key regulator of the brain 5-HT system 5-HT 1A receptor is under control of multiple factors [10,11] including transcriptional factors [12,13]. Freud-1 is one of the most important transcriptional factors for 5-HT 1A receptor gene.…”

Brain Beta-Catenin Signalling During Stress and Depression

“…It may be of note that 5-HT7 receptors have shown to display cross-reactivity with agonists for 5-HT1A, and both are highly expressed in regions of the brain related to depression during major depressive disorders [78]. …”

Papel dos receptores de glutamato do tipo NMDA localizados no Núcleo Mediano da Rafe na expressão do desamparo aprendido em ratos

“…Vários testes animais são utilizados para detectar efeitos antidepressivos e são baseados nas consequências comportamentais da exposição ao estresse incontrolável Outra possível explicação seria que os receptores 5-HT1A e 5-HT7 são co-expressos em muitos lugares no cérebro e estariam envolvidos na regulação de várias funções patológicas e fisiológicas (NAUMENKO et al, 2014). Além do mais, 5-HT7 serve como auto ou heterorreceptor (junto com 5-HT1A) na liberação de 5-HT nos núcleos da rafe, o que é, em parte, realizado pela neurotransmissão glutamatérgica (HARSING, 2006).…”