Janezic Eric M, Uppalapati Swetha, Nagl Stephanie, Contreras Marco, French Edward D, Fellous Jean-Marc
aComputational and Experimental Neuroscience Laboratory Departments of bPsychology cPharmacology, University of Arizona, Tucson, Arizona, USA.
Behav Pharmacol. 2016 Dec;27(8):704-717. doi: 10.1097/FBP.0000000000000270.
Post-traumatic stress disorder (PTSD) is in part due to a deficit in memory consolidation and extinction. Oxytocin (OXT) has anxiolytic effects and promotes prosocial behaviors in both rodents and humans, and evidence suggests that it plays a role in memory consolidation. We studied the effects of administered OXT and social co-housing in a rodent model of PTSD. Acute OXT yielded a short-term increase in the recall of the traumatic memory if administered immediately after trauma. Low doses of OXT delivered chronically had a cumulating anxiolytic effect that became apparent after 4 days and persisted. Repeated injections of OXT after short re-exposures to the trauma apparatus yielded a long-term reduction in anxiety. Co-housing with naive nonshocked animals decreased the memory of the traumatic context compared with single-housed animals. In the long term, these animals showed less thigmotaxis and increased interest in novel objects, and a low OXT plasma level. Co-housed PTSD animals showed an increase in risk-taking behavior. These results suggest beneficial effects of OXT if administered chronically through increases in memory consolidation after re-exposure to a safe trauma context. We also show differences between the benefits of social co-housing with naive rats and co-housing with other shocked animals on trauma-induced long-term anxiety.
创伤后应激障碍（PTSD）部分归因于记忆巩固和消退方面的缺陷。催产素（OXT）具有抗焦虑作用，并在啮齿动物和人类中促进亲社会行为，且有证据表明它在记忆巩固中发挥作用。我们在PTSD的啮齿动物模型中研究了给予OXT和群居的效果。如果在创伤后立即给予急性OXT，会使创伤记忆的回忆在短期内增加。长期给予低剂量的OXT具有累积抗焦虑作用，在4天后变得明显并持续存在。在短暂再次暴露于创伤装置后重复注射OXT可使焦虑长期减轻。与单笼饲养的动物相比，与未受惊吓的天真动物群居可降低对创伤情境的记忆。从长期来看，这些动物表现出较少的趋触性，对新物体的兴趣增加，且血浆OXT水平较低。群居的PTSD动物冒险行为增加。这些结果表明，如果通过在再次暴露于安全创伤情境后增强记忆巩固来长期给予OXT，会有有益效果。我们还展示了与未受惊吓的天真大鼠群居和与其他受惊吓动物群居在创伤诱导的长期焦虑方面的益处差异。
