Early-Life Blockade of 5-HT1A Receptors Alters Adult Anxiety Behavior and Benzodiazepine Sensitivity

摘要: Background Early-life stress may affect 5-HT1A receptor circuitry, which could result in increased anxiety later life. An phenotype KO mice (1AKO) has been ascribed to absence during the early postnatal period. Thus, subtle and transient serotonergic changes period lead an risk for developing stress-related disorders adulthood. Methods Wildtype 1AKO on a Swiss-Webster (SW) background were treated with vehicle or antagonist WAY-100,635. Results Pharmacologic blockade induced long-lasting effects benzodiazepine sensitivity adolescent adult resembles SW phenotype. Furthermore, WAY-100,635-treated had cortical gamma-aminobutyric acid-A (GABAAR) α1 α3 subunit levels hippocampal GABAAR α2 levels. Conclusions Absence of 5-HT1AR signaling stages brain maturation predisposes organism affective dysfunction Because early-life treatment WAY-100,635 reduced diazepam α prefrontal cortex hippocampus, our data suggest putative link between disruption system emergence decreased responsivity at age. Moreover, functionality appears be essential development normal functionality. This study have clinical implications psychoactive drug use pregnancy pharmacogenetic sensitivity.