Clinard Catherine T, Bader Lauren R, Sullivan Molly A, Cooper Matthew A
Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA.
Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA.
Neuropharmacology. 2015 Mar;90:102-12. doi: 10.1016/j.neuropharm.2014.11.016. Epub 2014 Nov 29.
Conditioned defeat is a model in Syrian hamsters (Mesocricetus auratus) in which normal territorial aggression is replaced by increased submissive and defensive behavior following acute social defeat. The conditioned defeat response involves both a fear-related memory for a specific opponent as well as anxiety-like behavior indicated by avoidance of novel conspecifics. We have previously shown that systemic injection of a 5-HT2a receptor antagonist reduces the acquisition of conditioned defeat. Because neural activity in the basolateral amygdala (BLA) is critical for the acquisition of conditioned defeat and BLA 5-HT2a receptors can modulate anxiety but have a limited effect on emotional memories, we investigated whether 5-HT2a receptor modulation alters defeat-induced anxiety but not defeat-related memories. We injected the 5-HT2a receptor antagonist MDL 11,939 (0 mM, 1.7 mM or 17 mM) or the 5-HT2a receptor agonist TCB-2 (0 mM, 8 mM or 80 mM) into the BLA prior to social defeat. We found that injection of MDL 11,939 into the BLA impaired acquisition of the conditioned defeat response and blocked defeat-induced anxiety in the open field, but did not significantly impair avoidance of former opponents in the Y-maze. Furthermore, we found that injection of TCB-2 into the BLA increased the acquisition of conditioned defeat and increased anxiety-like behavior in the open field, but did not alter avoidance of former opponents. Our data suggest that 5-HT2a receptor signaling in the BLA is both necessary and sufficient for the development of conditioned defeat, likely via modulation of defeat-induced anxiety.
条件性挫败是叙利亚仓鼠（金仓鼠）的一种行为模式，在经历急性社交挫败后，正常的领地攻击性会被增强的顺从和防御行为所取代。条件性挫败反应既涉及对特定对手的恐惧相关记忆，也包括通过回避陌生同类所表现出的类似焦虑的行为。我们之前已经表明，全身注射5-HT2a受体拮抗剂会减少条件性挫败的习得。由于基底外侧杏仁核（BLA）中的神经活动对于条件性挫败的习得至关重要，并且BLA中的5-HT2a受体可以调节焦虑，但对情绪记忆的影响有限，因此我们研究了5-HT2a受体调节是否会改变挫败诱导的焦虑，但不影响与挫败相关的记忆。在社交挫败前，我们将5-HT2a受体拮抗剂MDL 11,939（0 mM、1.7 mM或17 mM）或5-HT2a受体激动剂TCB-2（0 mM、8 mM或80 mM）注射到BLA中。我们发现，向BLA注射MDL 11,939会损害条件性挫败反应的习得，并在旷场实验中阻断挫败诱导的焦虑，但在Y迷宫实验中对回避先前对手的行为没有显著损害。此外，我们发现向BLA注射TCB-2会增加条件性挫败的习得，并在旷场实验中增加类似焦虑的行为，但不会改变对先前对手的回避。我们的数据表明，BLA中的5-HT2a受体信号传导对于条件性挫败的发展既是必要的也是充分的，可能是通过调节挫败诱导的焦虑来实现的。
