Harvey Brian H, Naciti Carla, Brand Linda, Stein Dan J
School of Pharmacy (Pharmacology), North-West University, Potchefstroom, 2520, South Africa.
Ann N Y Acad Sci. 2004 Dec;1032:267-72. doi: 10.1196/annals.1314.035.
Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain. Using a model of repeated trauma in rats, we observed significant spatial memory impairment together with significantly increased 5HT(1A) receptor density (B(max)), decreased 5HT(1A) receptor affinity (K(d)), and significantly increased 5HT(2A) receptor affinity on day 7 poststress. The serotonergic agent fluoxetine (FLX; 10 mg/kg/d ip) administered 1 week before stress and continuing throughout the stress procedure, but not the 5HT depleter p-chloro-phenylalanine (PCPA; 300/100/50 mg/kg/d ip), prevented stress-induced cognitive dysfunction. PCPA, however, reversed stress-induced hippocampal 5HT(1A) receptor affinity changes, with FLX narrowly missing significance. Neither drug reversed stress effects on 5HT(2A) receptor affinity. Thus, 5HT plays an important part in the cognitive-behavioral changes evoked by repeated trauma. That raised 5HT activity may mediate hippocampal 5HT(1A) receptor changes evoked by stress suggests a bidirectional role for 5HT in the development of PTSD.
创伤后应激障碍（PTSD）患者的海马体和前额叶皮质会出现结构变化，这些变化似乎与认知功能障碍相关。在这些脑区中，血清素（5HT）在PTSD的症状表现和治疗中起着重要作用。然而，5HT既具有致焦虑作用，也具有抗焦虑作用，虽然5HT再摄取抑制剂在治疗中有效，但5HT在PTSD发生过程中的作用仍不明确。通过大鼠重复创伤模型，我们观察到在应激后第7天，大鼠出现显著的空间记忆损伤，同时5HT（1A）受体密度（Bmax）显著增加、5HT（1A）受体亲和力（Kd）降低，以及5HT（2A）受体亲和力显著增加。在应激前1周给予血清素能药物氟西汀（FLX；10mg/kg/d，腹腔注射）并持续整个应激过程，但5HT耗竭剂对氯苯丙氨酸（PCPA；300/1百/50mg/kg/d，腹腔注射）则不能预防应激诱导的认知功能障碍。然而，PCPA可逆转应激诱导的海马体5HT（1A）受体亲和力变化，而FLX的作用则勉强未达显著水平。两种药物均不能逆转应激对5HT（2A）受体亲和力的影响。因此，5HT在重复创伤诱发的认知行为变化中起重要作用。5HT活性升高可能介导应激诱发的海马体5HT（1A）受体变化，这提示5HT在PTSD发生过程中具有双向作用。
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