Female oxytocin-deficient mice display enhanced anxiety-related behavior.
Previous studies have suggested that oxytocin (OT) may be anxiolytic in female laboratory rats and mice. The elevated plus-maze was used to compare anxiety-related behaviors of OT-deficient (OT-/-) and wild-type (OT+/+) mice. Female OT-/- mice displayed increased anxiety-related behavior compared with OT+/+ mice. The percentage of entries (P < 0.0002) and time spent (P < 0.003) in the open arms was less in female OT-/- than OT+/+ mice. Administration of synthetic OT, 2 ng by intracerebroventricular (icv) injection to female OT-/- mice, increased the percentage of entries (P < 0.003) and time spent (P < 0.004) in the open arms compared with artificial cerebrospinal fluid female OT-/- mice. Administration of an OT receptor antagonist (Atosiban, d[Dtyr(Et)(2), Thr(4)]ornithine vasotocin) 100 ng icv, to female OT+/+ mice increased anxiety-related behavior by decreasing the percentage of entries (P < 0.01) and time spent (P < 0.04) in the open arms compared with artificial cerebrospinal fluid-treated controls. Central infusion of an OT receptor antagonist, 100 ng icv, before administration of synthetic OT, 2 ng icv, in female OT-/- mice blocked the anxiolytic affect of OT. In contrast, male OT-/- mice displayed decreased anxiety-related behavior compared with male OT+/+ mice. The percentage of entries (P < 0.007) and time spent (P < 0.004) in the open arms was greater in male OT-/- vs. OT+/+ mice. Our findings indicate that OT pathways play a role in modulating anxiety in female mice of the C57BL/6 background, and the effect is mediated by the OT receptor.
Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. rcmst22@pitt.edu
Rose C
RC
Mantella
Regis R
RR
Vollmer
Xia
X
Li
Janet A
JA
Amico
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology*; D001522:Behavior, Animal; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010121:Oxytocin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000378:metabolism; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
D006727:Hormone Antagonists; D018045:Receptors, Oxytocin; C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin