بلوک گیرنده های GABA-A در دوره نوزادی فنوتیپ های رفتاری و فیزیولوژیکی را در موش های کوچک آزمایشگاهی بالغ تغییر می دهد(2017)

Title

Neonatal blockade of GABA-A receptors alters behavioral and physiological phenotypes in adult mice

English Abstract

Gamma-aminobutyric acid (GABA) plays an inhibitory role in the mature brain, and an excitatory role in the immature brain which affects proliferation, migration and differentiation of neurons during development. There is also increasing evidence suggesting that activation or blockade of the GABA-A receptors during early life can induce brain and behavioral abnormalities in adulthood. We investigated to determine whether neonatal blockade of the GABA-A receptors can alter anxiety- and depression-like behaviors, body weight, food intake, corticosterone and testosterone levels in adult mice. To this end, neonatal mice were treated with either DMSO or bicuculline (70, 150 and 300 µg/kg) during postnatal days 7, 9 and 11. When grown to adulthood, mice were exposed to behavioral tests to measure anxiety- (elevated plus-maze and light-dark box) and depression-like behaviors (tail suspension test and forced swim test). Stress-induced serum corticosterone and testosterone levels, body weight and food intake were also evaluated. Neonatal bicuculline exposure at dose of 300 µg/kg decreased anxiety-like behavior, stress-induced corticosterone levels and increased testosterone levels, body weight and food intake, without significantly influencing depression in adult male mice. However, no significant changes in these parameters were observed in adult females. These findings suggest that neonatal blockade of GABA-A receptors affects anxiety-like behavior, physiological and hormonal parameters in a sex-dependent manner in mice. Taken together, these data corroborate the concept that GABA-A receptors during early life have an important role in programming neurobehavioral phenotypes in adulthood.

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