¹National Cheng Kung University, Department of Physiology, Tainan, Taiwan, ²National Cheng Kung University, Institute of Behavioral Medicine, Tainan, Taiwan

Background: Oxytocin (OXT), a 9-amino acid neuropeptide, has been known for its social interaction- and stress-modulating effects. Emerging clinical and pre-clinical studies have revealed intranasal OXT administration may enhance social preferences.

Aims & Objectives: It remains unexplored whether robust stress and airborne OXT exposure may affect male mice's hetero-sex motives.

Method: Eight- to ten-week-old C57BL/6 male and female mice were used in this study. We first established male mice’ hetero-sex motive model in a 41 x 41 cm arena. Two ovariectomized (OVX) females were brought into heat (heat females) by using subcutaneous treatment with three daily injections of estrogen benzoate (EB, 0.5 μg/0.05 ml/injection) followed by one injection of progesterone (0.83 ng/0.05 ml), while remaining two OVX mice received equivalent volume of sesame oil serving as non-heat controls. Heat females were restrained in meshed cages on one-side corners, and the remaining two non-heat females were kept in same cages on opposite-side corners. Heat zone, thus, referred to one half of the arena containing two heat females’ corner, while non-heat zone the remaining half with non-heat female corners. Male mice were subjected to four conditions, including a tandem stressor vs. no stressor regimen and with vs. without the presence of airborne OXT (cotton tip impregnated with OXT (20 ug in 0.2 ml 2% ethanol-containing saline). “Tandem” stressor regimen consisted of 30-min unconditioned foot shocks followed by 30-min restraint in water. To assess long-term, rather than acute, effects of stress and airborne OXT exposure on male mice’ hetero-sex drives, their sex drives were assessed approximately 24 hours after the conclusion of the tandem stressor regimen and airborne OXT exposure.

Results: Our results showed that male mice receiving no stressor with and without airborne OXT exposure had high but comparable preference ratios [(time spent in heat zone – time spent in non-heat zone) / 600]. In contrast, stressed mice showed significantly lower ratios. The presentation of airborne OXT throughout the stressor regimen failed to affect such stress effects.

Discussion & Conclusions: We here report robust stress may significantly impair male mice’ hetero-sex drives.