Female mouse tears contain an anti-aggression pheromone

Tears contain pheromones that trigger specific behavioral responses. In the mouse, male tear fluid is involved in long and short-term effects such as the receptive behavior and pregnancy block in females and the aggression in males. In contrast, pup tears exert an inhibitory effect on male mating behavior, also promoting sexual rejection in females. In the rat, a male lacrimal protein acts as an intraspecific and heterospecific signal enhancing sexual behavior in females and evoking avoidance behavior in mouse. However, behavioral effects of female tears on male behavior have yet to be described. Here, we report that female lacrimal fluid of different mouse strains contains a relatively small and involatile factor that abolishes inter-male aggression switching it into a copulatory behavior. The production of this molecule by the lacrimal glands is not affected by the estrous cycle but it is sensitive to ovariectomy, thus suggesting a control mediated by hormones. Moreover, this lacrimal anti-aggression pheromone modulates the activity of the lateral habenula, a brain area responsible for the valence of the aggressive interactions.

Inhibition of stimulated lacrimal secretion by [D-Ala2]Met-enkephalinamide

The synthetic enkephalin analogue, [D-Ala2]Met-enkephalinamide (DALA) was used to investigate opioid peptide modulation of lacrimal protein secretion. By use of an in vitro perifusion system, the secretion of peroxidase by rat lacrimal gland fragments was measured during continuous stimulation for up to 60 min. DALA had no effect on unstimulated secretion of peroxidase. However, the addition of DALA to the perifusion medium resulted in a dose-dependent (10 nM-10 microM) inhibition of carbachol-stimulated peroxidase release. The maximum effect of DALA was achieved at a dose of 10 microM, which resulted in a 54% inhibition of carbachol-induced secretion. The opiate antagonist naloxone (10 nM-10 microM) did not alter basal or carbachol-stimulated peroxidase release. The effect on 10 microM carbachol-stimulated secretion by the addition of 3 microM DALA, however, was reversed in a dose-dependent manner by naloxone. The extent of inhibition of vasoactive intestinal peptidergic (VIPergic) stimulation (50 nM VIP) by DALA was similar to the inhibition of cholinergic stimulation of peroxidase release by gland fragments. Neither alpha 1-adrenergic stimulation of secretion nor a synergistic stimulation by VIP and carbachol was inhibited by the enkephalin analogue. We conclude that DALA exerts an inhibitory modulation of cholinergic and VIPergic stimulation of in vitro lacrimal protein secretion and suggest a physiological role for methionine enkephalin as an inhibitory peptide involved in the regulation of lacrimal gland function.