Lysophosphatidic acid (LPA) is a potent bioactive
lipid mediator with diverse biological properties. We previously found altered expression of the LPA-related genes in rodents
after treatment with
sertraline, which is widely used to treat
anxiety disorders and depression. However, little is known about the behavioral effects of LPA. In the present study, we investigated the behavioral effects of intracerebroventricular injection of LPA in adult mice. LPA did not significantly affect spontaneous locomotor activity, suggesting that LPA does not induce hyperactivity,
ataxia, or sedation. We next investigated the emotional effects of LPA via the hole-board test. LPA significantly increased the number of head-
dips in a dose- and time-related manner. A significant induction of head-dip counts occurred 15 and 30 min after LPA administration. To clarify the involvement of
LPA receptors, we examined the effect of the non-selective LPA1-4 receptor antagonist, 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (
BrP-LPA) co-administered with LPA.
BrP-LPA dose-dependently inhibited LPA-induced head-dip counts. We next investigated anxiety-like behavior via the elevated plus-maze test. LPA significantly reduced the percentage of time spent in the open arms and
BrP-LPA dose-dependently inhibited this anxiety-like behavior. In conclusion, LPA induced anxiety-like behavior in mice via
LPA receptors. Our results suggest that LPA signaling plays an important role in regulating anxiety in mice.