Early-life stress may affect 5-HT 1A receptor circuitry, which could result in increased anxiety in later life. An increased anxiety phenotype in 5-HT 1A receptor KO mice (1AKO) mice has been ascribed to 5-HT 1A receptor absence during the early postnatal period. Thus, subtle and transient serotonergic changes during the early postnatal period may lead to an increased risk for developing stress-related disorders during adulthood.Wildtype and 1AKO mice on a Swiss-Webster (SW) background were treated during the early postnatal period with vehicle or the 5-HT 1A receptor antagonist WAY-100,635.Pharmacologic 5-HT 1A receptor blockade during the early postnatal period induced long-lasting effects on anxiety and benzodiazepine sensitivity in adolescent and adult mice on a Swiss-Webster background and resembles the SW 1AKO phenotype. Furthermore, WAY-100,635-treated mice had increased cortical gamma-aminobutyric acid-A receptor (GABA A R) α 1 and α 3 subunit levels and increased hippocampal GABA A R α 2 subunit levels.Absence of 5-HT 1A R signaling during early stages of brain maturation predisposes an organism to affective dysfunction later in life. Because early-life treatment with WAY-100,635 in Swiss-Webster mice reduced diazepam sensitivity and increased GABA A R α subunit levels in the prefrontal cortex and hippocampus, our data suggest a putative link between early-life disruption of the serotonergic system and the emergence of increased anxiety and decreased benzodiazepine responsivity at adult age. Moreover, early-life 5-HT 1A receptor functionality appears to be essential for the development of normal GABA A R functionality. This study may have clinical implications for psychoactive drug use during pregnancy and for the pharmacogenetic background of benzodiazepine sensitivity.