The serotonin1A (5-HT1A) receptor is an important member of the superfamily of seven transmembrane domain G-protein coupled receptors (GPCRs). We report here that guanine nucleotide sensitivity of agonist binding to hippocampal 5-HT1A receptors is dependent on the concentration of Mg2+. Our results show that agonist binding to 5-HT1A receptors is relatively insensitive to guanine nucleotides in...

OBJECTIVE Given reports that (+/-)pindolol, a beta-adrenergic-5-HT1A/1B receptor antagonist, accelerates the onset of the therapeutic effect of certain antidepressant drugs in major depression, the aim of this study was to assess the effect of sustained (+/-)pindolol administration on the sensitivity of pre- and postsynaptic 5-HT1A receptors, terminal 5-HT1B autoreceptors and on overall 5-HT ne...

KEY POINTS In the dorsal raphe nucleus, it is known that serotonin release activates metabotropic 5-HT1A autoreceptors located on serotonin neurons that leads to an inhibition of firing through the activation of G-protein-coupled inwardly rectifying potassium channels. We found that in mouse brain slices evoked serotonin release produced a 5-HT1A receptor-mediated inhibitory postsynaptic curren...

Novel omega-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl derivatives 1-6 containing 4-, 5- and/or 6-arylsubstituted pyrid-2(1H)-one moiety were synthesized. All the new compounds were examined in vitro to assess their 5-HT1A and 5-HT2A receptor affinities. Compounds 3 and 4 with a 5- or a 6-phenylsubstituted pyridone ring demonstrated high 5-HT1A receptor affinity (Ki = 17 and 38 nM, respectively) ...

New arylpiperazines with a four-methylene spacer containing a terminal pyrimido[2,1-f] theophylline fragment were synthesized, and their 5-HT1A and 5-HT2A receptor affinities were determined. All these compounds displayed a high affinity for 5-HT1A receptors (Ki=0.5-21.5 nM), and low affinity for 5-HT2A ones. The results of in vivo experiments showed that compounds revealed potential agonistic ...

Several novel antipsychotics, such as aripiprazole, bifeprunox, SSR181507 [(3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine], and SLV313 [1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine], activate serotonin 5-hydroxytryptamine (5-HT)1A receptors. Such activity is associated with enhance...

The traditional Japanese medicine yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice....

A variety of studies have documented alterations in 5-HT1A receptor binding sites in the brain of subjects with major depressive disorder (MDD). The recently identified transcription factor, nuclear deformed epidermal autoregulatory factor (NUDR/Deaf-1) has been shown to function as a transcriptional modulator of the human 5-HT1A receptor gene. The present study was undertaken to document the r...

Several studies have demonstrated the involvement of 5-HT1A receptors in the pathogenesis of depression and in the antidepressant response to SSRIs. A functional new variant in the promoter region of the 5-HT1A gene was recently reported (-1019 C>G). The aim of this study is to investigate a possible association between this 5-HT1A receptor variant and antidepressant response to fluvoxamine in ...

In the present study, we have used wild-type and palmitoylation-deficient mouse 5-hydroxytryptamine(1A) receptor (5-HT1A) receptors fused to the yellow fluorescent protein- and the cyan fluorescent protein (CFP)-tagged alpha(i3) subunit of heterotrimeric G-protein to study spatiotemporal distribution of the 5-HT1A-mediated signaling in living cells. We also addressed the question on the molecul...