Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits.

The antidepressant-like activity of ketamine in the rat chronic mild stress model requires activation of cortical 5-HT1A receptors.

Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.

Serotonin 5-HT receptor biased agonists: The challenge of translating an innovative neuropharmacological concept into therapeutics.

Serotonin 5-HT receptor agonists are prime candidates for CNS drug discovery due to their involvement physiological and pathological processes relevant to neurology and psychiatry. However, the lack of target specificity of many previously characterized agonists has long been a barrier to pharmacological and therapeutic progress. Some of the obstacles may be overcome through the recent concept of biased agonism, which has attracted considerable attention to the development of novel chemical entities at 5-HT, and particularly 5-HT receptors, by specifically targeting intracellular signalling pathways that may themselves be linked to specific brain regions and therapeutic indications.

Fentanyl dose-sparing in polyarthritic rats requires full agonism at 5-HT receptors: Comparison between NLX-112, (±)8-OH-DPAT, and buspirone.

Background: NLX-112 (a.k.a.

Rapid reorganization of serotonin projections and antidepressant response to 5-HT1A-biased agonist NLX-101 in fluoxetine-resistant cF1ko mice.

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) like fluoxetine remain a first-line treatment for major depression, but are effective in less than half of patients and can take 4-8 weeks to show results. In this study, we examined cF1ko mice with genetically induced upregulation of 5-HT1A autoreceptors that reduces 5-HT neuronal activity. These mice display anxiety- and depression-related behaviors that did not respond to chronic fluoxetine treatment.