title: Chronic enhancement of brain oxytocin levels causes enduring anti-aggressive and pro-social explorative behavioral effects in male rats.
abstract: Oxytocin (OXT) has been implicated in the regulation of social behaviors, including intermale offensive aggression. Recently, we showed that acute enhancement of brain OXT levels markedly suppressed offensive aggression and increased social exploration in resident rats confronted with an intruder in their home territory. Moreover, a different responsivity to the exogenous OXTergic manipulation was observed among individuals based on their baseline aggression. In this study we aimed at evaluating the behavioral response to chronically enhancing or attenuating central OXT levels, and at scrutinizing whether the trait-aggression moderates the treatment-induced behavioral changes. To this end, resident male wild-type Groningen rats were continuously (via osmotic minipumps) intracerebroventricularly infused with synthetic OXT or a selective OXT receptor (OXTR) antagonist for 7days. Changes in behavior were assessed performing a resident-intruder test before and at the end of the treatment period, as well as after 7days of withdrawal. Chronic infusion of OXT was found to selectively suppress aggression and enhance social exploration. Chronic blockage of OXTRs instead increased introductory aggressive behavior (i.e. lateral threat), yet without affecting the total duration of the aggression. The magnitude of the anti-aggressive changes correlated positively with the level of baseline aggression. Interestingly, OXT-induced behavioral changes persisted 7days after cessation of the treatment. In conclusion, these findings provide further evidence that enhanced functional activity of the central OXTergic system decreases social offensive aggression while it increases social explorative behavior. The data also indicate that chronically enhancing brain OXT levels may cause enduring anti-aggressive and pro-social explorative behavioral effects.
authors.affiliation: Department of Behavioral Physiology, University of Groningen, 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: Department of Behavioral 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, 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, 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; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000601:surgery; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012919:Social Behavior; D013997:Time Factors
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: Chronic central infusion; Individual variability; Long-lasting effects; Offensive behavior; Osmotic minipump; Oxytocin; Social explorative behavior