Department of Clinical Sciences of Companion Animals, Division Anaesthesiology and Neurophysiology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.154, NL-3584 CM Utrecht, The Netherlands.
Eur J Pharmacol. 2010 Mar 10;629(1-3):58-62. doi: 10.1016/j.ejphar.2009.11.062. Epub 2009 Dec 1.
It was investigated whether continuous rate infusion of the alpha(2)-adrenoceptor agonist dexmedetomidine can suppress memory formation by mechanisms other than reducing perception of sensory input in a fear-conditioning paradigm. Different groups of rats infused with either saline or dexmedetomidine (2.0, 4.0 or 10.0microg/kg bolus, followed by 2.0, 4.0 or 10.0microg/kg/h continuous rate infusion respectively), were subjected to a somatosensory-evoked potential (SEP) fear-conditioning paradigm. This paradigm combined the pairing of an innoxious conditioned stimulus (CS) and a noxious unconditioned stimulus (US), of which the latter was used to generate the SEPs (training phase).The following day, the perception of the US during the training phase was assessed by presenting the CS only and subsequently scoring the resulting duration of freezing behaviour (testing phase). Freezing behaviour was reduced only in those groups which demonstrated reduced SEPs. Based on these findings, it is concluded that dexmedetomidine suppresses memory formation only at doses reducing central nervous system activity in response to sensory input.
研究了在恐惧条件反射模型中,通过减少感觉输入的感知以外的机制,连续输注α 2 -肾上腺素受体激动剂右美托咪定是否可以抑制记忆形成。分别用生理盐水或右美托咪定(2.0、4.0 或 10.0μg/kg 推注,然后分别以 2.0、4.0 或 10.0μg/kg/h 连续输注)输注的不同大鼠组,进行体感诱发电位(SEP)恐惧条件反射模型。该模型将无害条件刺激(CS)与有害非条件刺激(US)结合在一起,后者用于产生 SEP(训练阶段)。第二天,仅通过呈现 CS 来评估在训练阶段对 US 的感知,然后根据由此产生的冻结行为持续时间进行评分(测试阶段)。只有在 SEP 降低的那些组中,才会减少冻结行为。基于这些发现,可以得出结论,只有在降低中枢神经系统对感觉输入的反应的剂量下,右美托咪定才会抑制记忆形成。