Ovari Jelena, Leri Francesco
Department of Psychology, University of Guelph, 50 Stone Road East, Ontario, Canada.
Neurosci Lett. 2008 Oct 17;444(1):52-5. doi: 10.1016/j.neulet.2008.08.015. Epub 2008 Aug 8.
The purpose of this study was to investigate the role of the ventromedial prefrontal cortex (vmPFC) in the expression of extinguished heroin seeking as measured by conditioned place preference (CPP) in males Sprague-Dawley rats (n=25). Heroin place conditioning (0.3mg/kg SC x 4 sessions) was followed by a test of preference 24h later, extinction (saline x 4 sessions), heroin reconditioning (saline or 1.0mg/kg x 1 session), and a second test of place preference 24h later. Fifteen minutes prior to this test, rats received intra-vmPFC infusions (bilateral, 0.5 microl/side) of a mixture of GABA(A) (muscimol; 0.03 nmol) and a GABA(B) (baclofen; 0.3 nmol) agonists, or vehicle. As expected on the basis of previous studies, reconditioning with heroin resulted in the re-emergence of a CPP. Importantly, inactivation of the vmPFC produced the same effect in animals that did not receive heroin on the session of reconditioning. These results indicate that the vmPFC modulates expression of extinguished heroin seeking and suggest that prefrontal inhibitory mechanisms are involved in relapse to drug seeking.
本研究旨在探讨腹内侧前额叶皮质(vmPFC)在雄性Sprague-Dawley大鼠(n = 25)中通过条件性位置偏爱(CPP)测量的消退海洛因觅求行为表达中的作用。进行海洛因位置条件化(0.3mg/kg皮下注射×4次),24小时后进行偏爱测试,然后进行消退训练(生理盐水×4次)、海洛因重新条件化(生理盐水或1.0mg/kg×1次),24小时后进行第二次位置偏爱测试。在该测试前15分钟,大鼠接受双侧腹内侧前额叶皮质注射(每侧0.5微升)GABA(A)(蝇蕈醇;0.03纳摩尔)和GABA(B)(巴氯芬;0.3纳摩尔)激动剂的混合物或溶剂。基于先前研究预期,用海洛因重新条件化导致CPP再次出现。重要的是,在重新条件化阶段未接受海洛因的动物中,腹内侧前额叶皮质失活产生了相同的效果。这些结果表明,腹内侧前额叶皮质调节消退的海洛因觅求行为的表达,并提示前额叶抑制机制参与了复吸觅药行为。