Altered brain serotonin 5-HT receptor expression and function in juvenile Fmr1 knockout mice.

There are no approved pharmacotherapies for fragile X syndrome (FXS), a rare neurodevelopmental disorder caused by a mutation in the FMR1 promoter region that leads to various symptoms, including intellectual disability and auditory hypersensitivity. The gene that encodes inhibitory serotonin 1A receptors (5-HTRs) is differentially expressed in embryonic brain tissue from individuals with FXS, and 5-HTRs are highly expressed in neural systems that are disordered in FXS, providing a rationale to focus on 5-HTRs as targets to treat symptoms of FXS. We examined agonist-labeled 5-HTR densities in male and female Fmr1 knockout mice and found no differences in whole-brain 5-HTR expression in adult control compared to Fmr1 knockout mice.

The Psychedelic ,-Dipropyltryptamine Prevents Seizures in a Mouse Model of Fragile X Syndrome via a Mechanism that Appears Independent of Serotonin and Sigma1 Receptors.

The serotonergic psychedelic psilocybin shows efficacy in treating neuropsychiatric disorders, though the mechanism(s) underlying its therapeutic effects remain unclear. We show that a similar psychedelic tryptamine, ,-dipropyltryptamine (DPT), completely prevents audiogenic seizures (AGS) in an knockout mouse model of fragile X syndrome at a 10 mg/kg dose but not at lower doses (3 or 5.6 mg/kg).

FPT, a 2-Aminotetralin, Is a Potent Serotonin 5-HT, 5-HT, and 5-HT Receptor Agonist That Modulates Cortical Electroencephalogram Activity in Adult Knockout Mice.

There are no approved medicines for fragile X syndrome (FXS), a monogenic, neurodevelopmental disorder. Electroencephalogram (EEG) studies show alterations in resting-state cortical EEG spectra, such as increased gamma-band power, in patients with FXS that are also observed in knockout models of FXS, offering putative biomarkers for drug discovery. Genes encoding serotonin receptors (5-HTRs), including 5-HT, 5-HT, and 5-HTRs, are differentially expressed in FXS, providing a rationale for investigating them as pharmacotherapeutic targets.

Spontaneous seizures in adult Fmr1 knockout mice: FVB.129P2-Pde6bTyrFmr1/J.

The prevalence of seizures in individuals with fragile X syndrome (FXS) is ~25%; however, there are no reports of spontaneous seizures in the Fmr1 knockout mouse model of FXS. Herein, we report that 48% of adult (median age P96), Fmr1 knockout mice from our colony were found expired in their home cages. We observed and recorded adult Fmr1 knockout mice having spontaneous convulsions in their home cages.

Evaluation of lorcaserin as an anticonvulsant in juvenile Fmr1 knockout mice.

Recent preclinical and clinical studies suggest that lorcaserin, a preferential serotonin 2C receptor (5-HTR) agonist that was approved for the treatment of obesity, possesses antiepileptic properties. Here, we tested whether lorcaserin (1, 3, 5.6, 10 mg/kg) is prophylactic against audiogenic seizures (AGSs) in juvenile Fmr1 knockout mice, a mouse model of fragile X syndrome (FXS).

()-5-(2'-Fluorophenyl)-,-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, a Serotonin Receptor Modulator, Possesses Anticonvulsant, Prosocial, and Anxiolytic-like Properties in an Knockout Mouse Model of Fragile X Syndrome and Autism Spectrum Disorder.

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities and a plethora of neuropsychiatric symptoms. FXS is the leading monogenic cause of autism spectrum disorder (ASD), which is defined clinically by repetitive and/or restrictive patterns of behavior and social communication deficits. Epilepsy and anxiety are also common in FXS and ASD.