Altered brain serotonin 5-HT < sub > 1A < /sub > receptor expression and function in juvenile Fmr1 knockout mice

We examined agonist-labeled 5-HT1AR densities in male and female Fmr1 knockout mice, a mouse model of FXS, and found no difference in whole-brain 5-HT1AR expression in adult control compared to Fmr1 knockout mice. However, juvenile Fmr1 knockout mice had significantly lower whole-brain 5-HT1AR expression than age-matched controls. Consistent with these results, juvenile Fmr1 knockout mice showed significantly reduced behavioral responses elicited by the 5-HT1AR agonist (R)-8-OH-DPAT, effects blocked by the selective 5-HT1AR antagonist, WAY-100635. Also, treatment with the selective 5-HT1AR agonist, NLX-112, dose-dependently prevented audiogenic seizures (AGS) in juvenile Fmr1 knockout mice, an effect reversed by WAY-100635. Suggestive of a central role for 5-HT1ARs in regulating AGS, compared to males, female Fmr1 knockout mice showed a lower prevalence of AGS and higher expression of antagonist-labeled 5-HT1ARs in the inferior colliculus, a neural system necessary for AGS. These results provide preclinical support that 5-HT1AR agonists may be therapeutic for young individuals with FXS hypersensitive to auditory stimuli.PMID:37923121 | DOI:10.1016/j.neuropharm.2023.109774
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Source Type: research