Jacobson-Pick Shlomit, Elkobi Alina, Vander Shelly, Rosenblum Kobi, Richter-Levin Gal
The Brain & Behavior Research Center, University of Haifa, Mount Carmel, 31905 Haifa, Israel.
Int J Neuropsychopharmacol. 2008 Nov;11(7):891-903. doi: 10.1017/S1461145708008559. Epub 2008 Mar 25.
Profound evidence indicates that GABAA receptors are important in the control of physiological response to stress and anxiety. The alpha subunit type composition contributes significantly to the functional characterization of the GABAA receptors. The alpha2, alpha3, alpha5 subunits are predominately expressed in the brain during embryonic and early postnatal periods of normal rats, whilst alpha1 are most prominent during later developmental stages. In the present study, we examined the long-term effects of juvenile stress on GABA alpha subunit expression in adulthood in the amygdala and hippocampus. We applied the elevated platform stress paradigm at juvenility and used the open-field and startle response tests to assess anxiety level in adulthood. Juvenile stress effects without behavioural tests in adulthood were also examined since previous studies indicated that the mere exposure to these tests might be stressful for rats, enhancing the effects of the juvenile exposure to stress. In adulthood, we quantitatively determined the level of expression of alpha1, alpha2 and alpha3 in the hippocampus and amygdala. Our results indicate that subjecting juvenile stressed rats to additional challenges in adulthood results in an immature-like expression profile of these subunits. To test for potential functional implications of these alterations we examined the effects of the anxiolytic (diazepam) and the sedative (brotizolam) benzodiazepines on juvenile stressed and control rats following additional challenges in adulthood. Juvenile stressed rats were more sensitive to diazepam and less sensitive to brotizolam, suggesting that the alterations in GABA alpha subunit expression in these animals have functional consequences.
确凿证据表明，GABAA受体在控制对应激和焦虑的生理反应中起重要作用。α亚基类型组成对GABAA受体的功能特性有显著贡献。在正常大鼠的胚胎期和出生后早期，α2、α3、α5亚基在大脑中大量表达，而α1亚基在发育后期最为突出。在本研究中，我们研究了幼年应激对成年大鼠杏仁核和海马体中GABAα亚基表达的长期影响。我们在幼年时应用高架平台应激范式，并使用旷场试验和惊吓反应试验来评估成年期的焦虑水平。由于先前的研究表明，仅仅接受这些测试可能会给大鼠带来压力，从而增强幼年应激的影响，因此我们还研究了无成年期行为测试的幼年应激效应。在成年期，我们定量测定了海马体和杏仁核中α1、α2和α3的表达水平。我们的结果表明，幼年应激大鼠在成年期面临额外挑战会导致这些亚基呈现类似未成熟的表达模式。为了测试这些改变的潜在功能影响，我们研究了抗焦虑药（地西泮）和镇静药（溴替唑仑）苯二氮䓬类药物对成年期面临额外挑战的幼年应激大鼠和对照大鼠的影响。幼年应激大鼠对地西泮更敏感，对溴替唑仑不敏感，这表明这些动物中GABAα亚基表达的改变具有功能后果。
