Subacute fluoxetine enhances conditioned responding and conditioning-specific reflex modification of the rabbit nictitating membrane response: implications for drug treatment with selective serotonin reuptake inhibitors.
Subacute fluoxetine enhances conditioned responding and conditioning-specific reflex modification of the rabbit nictitating membrane response: implications for drug treatment with selective serotonin reuptake inhibitors.
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DOI：
10.1097/fbp.0b013e32835d528e
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发表时间：
2013-02
影响因子：
1.6
通讯作者：
Schreurs BG
中科院分区：
文献类型：
--
作者：
Burhans LB;Smith-Bell CA;Schreurs BG
对兔瞬膜反应（NMR）的大量研究表明，在经典恐惧条件反射后，NMR反射会变得夸张。这种与学习相关的变化被称为条件特异性反射改变（CRM），并且在没有条件刺激的情况下也能观察到。本研究的目的是检验CRM范式对使用氟西汀进行的血清素能调控的敏感性，氟西汀是一种常用于治疗焦虑症的选择性血清素再摄取抑制剂。为了评估氟西汀对表明CRM的夸张反射反应以及对条件性线索恐惧的影响，兔子接受了延迟NMR条件反射（声音和眶周电击配对），并进行CRM测试，随后每天注射氟西汀（0.03、0.3或3.0 mg/kg）或生理盐水，持续5天。在1天和1周后重新评估CRM，然后对声音的条件反应（CRs）进行保持性测试。在治疗停止一周后，氟西汀（3.0 mg/kg）增强了CRM和条件反应的保持，这与其他动物模型和人类中焦虑样行为增加的报道一致。因此，CRM范式可能为理解选择性血清素再摄取抑制剂的矛盾效应背后的机制提供重要见解。
Extensive research on the rabbit nictitating membrane response (NMR) has shown that the NMR reflex can become exaggerated following classical fear conditioning. This learning-related change is referred to as conditioning-specific reflex modification (CRM) and is observed in the absence of the conditioned stimulus. The aim of the current study was to examine the sensitivity of the CRM paradigm to serotonergic manipulation with fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor for anxiety disorders. To assess the effect of fluoxetine on exaggerated reflexive responding indicative of CRM and on conditioned cued fear, rabbits underwent delay NMR conditioning (pairings of tone and periorbital shock) and were tested for CRM, followed by 5 days of daily fluoxetine (0.03, 0.3, or 3.0 mg/kg) or saline injections. CRM was reassessed 1 day and 1 week later, followed by a retention test of conditioned responses (CRs) to the tone. Fluoxetine (3.0 mg/kg) enhanced CRM and retention of conditioned responses, a week after treatment ceased, and this is in agreement with the reports on increased anxiety-like behaviors in other animal models and humans. The CRM paradigm, therefore, may provide important insight into the mechanisms underlying the paradoxical selective serotonin reuptake inhibitor effects.