Fig. 3: Endogenous OXT promotes, whereas synthetic AVP and OXT reduce aggression in females.

a Experimental design for pharmacological and chemogenetic experiments targeting the OXT and AVP systems in isolated and trained (IST) and group-housed (GH) rats. (AAV adeno-associated DREADD virus infusion into the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei; AVP arginine vasopressin; arrow=drug infusions; FIT female intruder test, IS social isolation, OXT oxytocin, OXTR-A OXT receptor antagonist, SURG surgery, V1aR-A V1a receptor antagonist, WO wash-out). b i.c.v. infusion of OXT (50 ng/5 µl) increased aggression in GH (two-tailed Student’s t test t(19) = 2.46, p = 0.024), c but decreased aggression in IST females (t(8) = 2.33, p = 0.048, data corresponds to FIT4 and 6). d i.c.v. infusion of V1aR-A (750 ng/5 µl), but not OXTR-A (750 ng/5 µl), blocked the anti-aggressive effects of OXT in IST females (one-way ANOVA followed by Bonferroni F(3,28) = 10.1, p = 0.001). Also, the V1aR-A alone did not affect aggression. Both, e i.c.v. infusion of OXTR-A (t(28) = 4.96, p < 0.0001) and f i.c.v. AVP (0.1 or 1 ng/5 µl) reduced total aggressive behavior (F(3,54) = 7.48, p = 0.0003) in IST rats. g Chemogenetic activation of OXT neurons in the PVN and SON increased aggression only in metestrus-diestrus GH rats (two-way ANOVA, factor treatment: F(1,19) = 3.342, p = 0.083; estrous cycle: F(1,19) = 6.68, p = 0.018; treatment × estrous cycle: F(1,19) = 6.45, p = 0.02). h Confirmation of virus infection in the PVN (right) and SON (left). OXT-neurophysin I staining: green; mCherry (virus): red. Scale bars 300 µm. Data are shown as mean+SEM. *p < 0.05; **p < 0.01; ***p < 0.0001 vs either vehicle or control; ep < 0.05 vs met-diestrus. OXT: GH: n = 9 and 12; IST: n = 9; AVP: n = 18, 9, and 9, respectively; OXTR-A: n = 14 and 15; combination OXT/OXTR-A/V1aR-A: n = 8, 6, 8, 9, and 7, respectively; chemogenetics: n = 6 and 15. Control group consisted of (i) rAAV1/2 OXTpr-mCherry+CNO, no virus infusion + (ii) saline, or (iii) CNO.