Department of Pharmacology of the School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
Eur Neuropsychopharmacol. 2013 Nov;23(11):1611-22. doi: 10.1016/j.euroneuro.2012.11.002. Epub 2012 Nov 30.
In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. The treatment of the PVN with LY235959 also reduced the increase in plasma corticosterone levels during stress and inhibited the anxiogenic-like effect observed in the elevated plus-maze 24h after the restraint session. The present results show that NMDA and non-NMDA receptors in the PVN differently modulate responses associated to stress. The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress.
在本研究中，研究了下丘脑室旁核（PVN）谷氨酸受体在调节自主神经（动脉血压、心率和尾巴皮肤温度）和神经内分泌（血浆皮质酮）反应以及急性束缚应激引起的行为后果中的作用。将选择性非 NMDA 谷氨酸受体拮抗剂 NBQX（2 nmol/100 nL）双侧微注射到 PVN 中，可减少动脉血压升高以及束缚应激引起的尾巴皮肤温度下降，而不影响应激引起的心动过速反应。另一方面，PVN 用选择性 NMDA 谷氨酸受体拮抗剂 LY235959（2 nmol/100 nL）预处理能够增加应激引起的升压和心动过速反应，而不影响尾巴皮肤温度的下降。LY235959 处理 PVN 还降低了应激期间血浆皮质酮水平的升高，并抑制了束缚后 24 小时在高架十字迷宫中观察到的焦虑样效应。目前的结果表明，PVN 中的 NMDA 和非 NMDA 受体不同地调节与应激相关的反应。PVN 谷氨酸能神经传递通过非 NMDA 受体对应激引起的自主神经反应具有促进作用。另一方面，本数据表明 PVN NMDA 受体对心血管对应激的反应具有抑制作用。此外，我们的发现还表明，PVN NMDA 谷氨酸受体参与了应激引起的血浆皮质酮反应以及应激引起的延迟性情绪后果的介导。
