title: Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats.
abstract: 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.
authors.affiliation: Department of Behavioral Physiology, University of Groningen, Nijenborgh 7, P.O. Box 11103, 9700 CC Groningen, The Netherlands. Electronic address: f.calcagnoli@rug.nl.
authors.forename: Federica
authors.initials: F
authors.lastname: Calcagnoli
authors.affiliation: Behavioral Neuroscience Group, School of Psychology, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Stubbendorff
authors.affiliation: Department of Behavioural Biology, University of Muenster, Badestr. 13, 48149 Muenster, Germany.
authors.forename: Neele
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Department of Behavioral Physiology, University of Groningen, Nijenborgh 7, P.O. Box 11103, 9700 CC Groningen, The Netherlands.
authors.forename: Sietse F
authors.initials: SF
authors.lastname: de Boer
authors.affiliation: Department of Child and Adolescent Psychiatry, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Monika
authors.initials: M
authors.lastname: Althaus
authors.affiliation: Department of Behavioral Physiology, University of Groningen, Nijenborgh 7, P.O. Box 11103, 9700 CC Groningen, The Netherlands.
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Koolhaas
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D002408:Catheters, Indwelling; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000502:physiology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D010121:Oxytocin / Q000008:administration & dosage / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D018045:Receptors, Oxytocin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001892:Camphanes; D002491:Central Nervous System Agents; D010879:Piperazines; D018045:Receptors, Oxytocin; D010121:Oxytocin; C086206:L 368899
keywords: Central amygdala; Dorsal raphe; Intermale offensive behavior; Oxytocin; Social exploration