Galanin subtype 1 and subtype 2 receptors mediate opposite anxiety-like effects in the rat dorsal raphe nucleus

<p>Galanin Receptors as Drug Target for Novel Antidepressants: Review</p>

“…61,62 The pro-depressant effect of GalR1 is attributed to its ability to modulate 5-Hydroxytryptamine-1A (5-HT1AR) signaling owing to its hyperpolarizing and ability of forming a complex with 5-HT1AR to inhibit release and binding, and reduction of serotonin metabolism in ventral limbic cortex, the hippocampal formation, and frontal parietal cortex. 52 The interaction of GALRs with 5-HT1A receptors was found in the paraventricular thalamic nucleus, the nucleus reuniens and rhomboideus, the zona incerta, the medial and the lateral hypothalamus, and the medial and the lateral amygdaloid area, but not in the pars compacta of the substantia nigra, which lacks 5-HT1AR binding sites. 63 The binding characteristics of the neuropeptide were analyzed on 5-HT receptor subtypes in the ventral limbic cortex of the rat; 52 and it has been demonstrated that GalR1-5-HT1AR heteromerize.…”

“…52 The interaction of GALRs with 5-HT1A receptors was found in the paraventricular thalamic nucleus, the nucleus reuniens and rhomboideus, the zona incerta, the medial and the lateral hypothalamus, and the medial and the lateral amygdaloid area, but not in the pars compacta of the substantia nigra, which lacks 5-HT1AR binding sites. 63 The binding characteristics of the neuropeptide were analyzed on 5-HT receptor subtypes in the ventral limbic cortex of the rat; 52 and it has been demonstrated that GalR1-5-HT1AR heteromerize. 64 It was found that GAL markedly decreased the affinity value of 5-HT1AR binding, while there were no effects on the binding characteristics of the 5-HT1B or 5-HT2 radio ligands.…”

“…[43][44][45][46][47] Recent studies have shown the interaction of serotonergic system and neuropeptides to be a key aspect of implication to treat major depression in rodents. [48][49][50] In depression, the neuropeptide modulates the release of neurotransmitters from the LC 51 and raphe nucleus 52,53 through signal transduction mediated by GalRs (1-3). 54 Involvement of GalR1 was explored in a rat model of depression based on chronic mild stress.…”

“…This GalR1-5-HT1AR interaction is located in dorsal raphe 5-HT1AR cells that innervate large parts of forebrain. 52,53 Thus, GAL upon receptor-receptor interaction with 5-HT1AR induces hyperpolarization of serotonergic neurons it reduces the binding affinity of post-junctional and serotonin autoreceptor. Its binding to GalR1 receptor subtype causes GalR1-5-HT1AR activation via Gi/o-AC-PKA cascades, thereby decreasing the phosphorylation of cyclic AMP response element binding protein (CREB) that leads to a reduced gene transcription such as anti-apoptotic proteins.…”

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

“…The ability to activate GALR2, specifically, had interesting therapeutic possibilities as each subtype of GALRs has been found to exhibit largely divergent physiological function. For instance, a recent observation demonstrates that GALR1 and GALR2 mediate opposite anxiety-like effects in rats: GALR1 and GALR2 agonists exerted anxiogenic and anxiolytic-like effects, respectively (Morais et al ., 2016). GALR3 may also induce anxiogenic behaviour as GALR3-specific antagonists decrease anxiety and induce depression-like behavior in rats (Swanson et al ., 2005).…”