Laboratory of Biological Psychology, Department of Psychology, University of Leuven, Tiensestraat 102, 3000 Leuven, Belgium.
Psychopharmacology (Berl). 2009 Oct;206(3):389-401. doi: 10.1007/s00213-009-1614-4. Epub 2009 Jul 22.
The effects of pre-conditioning administration of anxiolytic benzodiazepines on the acquisition of a conditioned taste aversion (CTA) and on the acquisition of attenuation of neophobia (AN) were investigated in C57BL/6 mice.
A CTA was induced by injecting lithium chloride (LiCl; 6 mEq x kg(-1)) 30 min after the animal had imbibed a novel 0.5% saccharin solution. In other animals, neophobia was attenuated by a single access to the novel 0.5% saccharin solution, followed only by injection of saline.
Pre-conditioning administration of chlordiazepoxide (CDZ; 6-24 mg x kg(-1), i.p.) and alprazolam (0.3-1 mg x kg(-1), p.o.) resulted in a CTA that did not differ initially from that observed in vehicle-treated controls, but which showed faster extinction. The acquisition of AN was impaired only after the higher doses of CDZ (12-24 mg x kg(-1), i.p.) or alprazolam (1 mg x kg(-1), i.p.). The results show that in this test, altered acquisition of an aversive CTA memory by anxiolytic benzodiazepines is reflected in more rapid extinction. Moreover, at low doses, these drugs showed selectivity for weakening CTA learning compared to AN learning. Evidence is discussed that selective weakening of aversive memory formation is a clinically relevant effect of anxiolytic benzodiazepines.
本研究旨在探讨苯二氮䓬类抗焦虑药物预先给药对条件味觉厌恶（CTA）习得和新异回避（AN）习得衰减的影响。
通过在动物饮用新的 0.5% 蔗糖溶液 30 分钟后注射氯化锂（LiCl；6 mEq x kg(-1))来诱导 CTA。在其他动物中，通过单次接触新的 0.5% 蔗糖溶液来减轻新异回避，然后仅注射盐水。
预先给予地西泮（CDZ；6-24 mg x kg(-1)，ip）和阿普唑仑（0.3-1 mg x kg(-1)，po）可导致 CTA，最初与对照组无差异，但消退更快。只有在较高剂量的 CDZ（12-24 mg x kg(-1)，ip）或阿普唑仑（1 mg x kg(-1)，ip）时，才会损害 AN 的习得。结果表明，在该测试中，抗焦虑苯二氮䓬类药物改变了对厌恶 CTA 记忆的获得，反映在更快的消退上。此外，在低剂量下，这些药物对 CTA 学习的削弱表现出选择性，而不是对 AN 学习的削弱。有证据表明，选择性削弱厌恶记忆的形成是抗焦虑苯二氮䓬类药物的一种临床相关效应。
