Calcagnoli Federica, Stubbendorff Christine, Meyer Neele, de Boer Sietse F, Althaus Monika, Koolhaas Jaap M
Department of Behavioral Physiology, University of Groningen, Nijenborgh 7, P.O. Box 11103, 9700 CC Groningen, The Netherlands.
Behavioral Neuroscience Group, School of Psychology, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
Neuropharmacology. 2015 Mar;90:74-81. doi: 10.1016/j.neuropharm.2014.11.012. Epub 2014 Nov 29.
We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the present study, we targeted two critical brain areas, i.e. the central amygdala (CeA) and the dorsal raphe (DR), both containing high levels of OXT receptors (OXTRs) and constituting important nodes of the neural circuitry related to aggression. Behavioral effects of local micro-infusion of OXT and OXTR antagonist, L368.899, (alone and combined) were evaluated in resident male rats during confrontations with an unfamiliar male intruder. Our results show that OXT microinjected into the CeA markedly reduced resident's offensive behavior and facilitated social exploration, without affecting other non-aggressive behaviors. The receptor specificity of the behavioral effects was verified when a micro-infusion of a selective OXTR antagonist nullified the changes. Pharmacological blockade of CeA OXTRs per se was without clear behavioral effects suggesting that endogenous OXT within the CeA does not play a major inhibitory role on offensiveness. Anatomical specificity was also supported by the absence of relevant behavioral effects when OXT was microinjected into more medial sub-regions of the amygdala. Likewise, within the DR neither OXT nor OXTR exerted significant effects on offensive aggression, while microinjection of the 5-HT1A autoreceptor agonist in this region significantly suppressed aggression. In conclusion, our results point at the CeA as an important brain site of action for the anti-aggressive and pro-social explorative effects induced by exogenous enhancement of brain OXT levels.
我们最近证明,急性和慢性脑室内增强脑内催产素(OXT)水平可在社交挑战期间诱导强大的抗攻击和亲社会探索效应。然而,OXT发挥作用的确切脑内解剖位置仍不清楚。在本研究中,我们针对两个关键脑区,即中央杏仁核(CeA)和中缝背核(DR),这两个区域都含有高水平的OXT受体(OXTRs),并且是与攻击相关的神经回路的重要节点。在与陌生雄性入侵者对抗期间,对成年雄性大鼠局部微量注射OXT和OXTR拮抗剂L368.899(单独和联合)的行为效应进行了评估。我们的结果表明,向CeA微量注射OXT可显著降低大鼠的攻击行为并促进社交探索,而不影响其他非攻击行为。当微量注射选择性OXTR拮抗剂消除这些变化时,验证了行为效应的受体特异性。CeA中OXTRs的药理学阻断本身没有明显的行为效应,这表明CeA内的内源性OXT对攻击性没有主要抑制作用。当OXT被微量注射到杏仁核更内侧的子区域时,没有相关行为效应,这也支持了解剖学特异性。同样,在DR内,OXT和OXTR对攻击行为均未产生显著影响,而在此区域微量注射5-HT1A自身受体激动剂可显著抑制攻击行为。总之,我们的结果表明,CeA是脑内OXT水平外源性增强所诱导的抗攻击和亲社会探索效应的重要作用脑区。