Department of Pharmacology, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Br J Pharmacol. 2012 Sep;167(1):207-21. doi: 10.1111/j.1476-5381.2012.01985.x.
The bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats.
Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty-four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re-exposure to the aversive context.
L-propranolol, a non-selective β-adrenoceptor antagonist, and phentolamine, a non-selective α-adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective β(1) -adrenoceptor antagonist, and WB4101, a selective α(1) -antagonist, but not with ICI118,551, a selective β(2) -adrenoceptor antagonist or RX821002, a selective α(2) -antagonist.
These findings support the idea that noradrenergic neurotransmission in the BNST via α(1) - and β(1) -adrenoceptors is involved in the expression of conditioned contextual fear.
终纹床核(BNST)是边缘系统的一个结构,参与条件性情境恐惧的表达。在 BNST 的众多神经传入中,去甲肾上腺素能突触末梢是突出的,一些证据表明,在厌恶情境中 BNST 中的这种去甲肾上腺素能神经传递被激活。在这里,我们研究了 BNST 去甲肾上腺素能系统在调节大鼠条件性情境恐惧诱导的行为和自主反应中的作用。
双侧 BNST 植入套管的雄性 Wistar 大鼠接受 10 分钟的条件性训练(6 次电击,1.5mA/3s)。24 小时后,测量大鼠对条件箱的冻结和自主反应(平均动脉压、心率和皮肤温度)10 分钟。在重新暴露于厌恶环境之前 10 分钟给予肾上腺素能受体拮抗剂。
非选择性β-肾上腺素受体拮抗剂 L-普萘洛尔和非选择性α-肾上腺素受体拮抗剂酚妥拉明可减少厌恶环境诱导的冻结和自主反应。选择性β(1)-肾上腺素受体拮抗剂 CGP20712 和选择性α(1)-拮抗剂 WB4101 也观察到类似的结果,但选择性β(2)-肾上腺素受体拮抗剂 ICI118551 或选择性α(2)-拮抗剂 RX821002 则没有。
这些发现支持了 BNST 中的去甲肾上腺素能神经传递通过α(1)-和β(1)-肾上腺素受体参与条件性情境恐惧表达的观点。