Spinal transection switches the effect of metabotropic glutamate receptor subtype 7 from the facilitation to inhibition of ejaculation

Abstract Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which localize to presynaptic active zones of the central nervous system. We previously reported that mGluR7 knockout (KO) mice exhibit ejaculatory disorders, although they have normal sexual motivation. We hypothesized that mGluR7 regulates ejaculation by potentiating the excitability of the neural circuit in the lumbosacral spinal cord, because administration of the mGluR7-selective antagonist into that region inhibits drug-induced ejaculation. In the present study, to elucidate the mechanism of impaired ejaculation in mGluR7 KO mice, we eliminated the influence of the brain by spinal transection (spinalization). Unexpectedly, sexual responses of mGluR7 KO mice were stronger than those of wild-type mice after spinalization. Histological examination indicated that mGluR7 controls sympathetic neurons as well as parasympathetic neurons. In view of the complexity of its synaptic regulation, mGluR7 might control ejaculation by multi-level and multi-modal mechanisms. Our study provides insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.