Guimarães F S, Del Bel E A, Padovan C M, Netto S M, de Almeida R T
Department of Pharmacology, School of Medicine, Ribeirão Preto, SP, Brazil.
Behav Brain Res. 1993 Dec 20;58(1-2):133-9. doi: 10.1016/0166-4328(93)90098-b.
It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.
有人提出，海马体中的突触后5-HT1A受体由位于中缝核的5-HT神经元支配，介导对厌恶事件的适应性或应对反应，且该系统功能障碍与抑郁症状有关。为了验证这一假设，我们研究了遭受固定应激的动物中c-fos mRNA的表达。结果显示，强制约束30分钟后，海马齿状回和CA1-CA3区域的c-fos mRNA表达显著增加，表明该结构在应激期间被激活。为了研究海马体中5-HT神经传递在适应厌恶事件中的作用，我们将大鼠固定2小时，并在24小时后在高架十字迷宫中对它们进行测试。我们的结果显示，先前的约束期会减少大鼠在迷宫中对开放臂的探索。在约束后立即向背侧海马体双侧微量注射齐美利定（20和100 nmol），一种5-HT再摄取阻滞剂，或8-OH-DPAT（3 nmol），一种5-HT1A激动剂，可逆转这种效应。这些结果与海马体中突触后5-HT1A受体参与对厌恶事件耐受性形成的观点一致。
