Enhanced effect of the hallucinogen DOI in L-DOPA receptor Gpr143-deficient mice.
Journal of pharmacological sciences June 1, 2026 Daiki Masukawa, Rei Tajika, Yoshimi Ichimaru et al.
Hallucinogens like LSD act mainly through the 5-HT2A receptor, but how they are regulated is not fully understood. GPR143, a receptor for L-DOPA, modulates certain other receptors. In mice lacking GPR143, the hallucinogen DOI caused more hyperactivity and more c-Fos expression in the nucleus accumbens, indicating enhanced effects. In cells expressing the 5-HT2A receptor, adding GPR143 reduced DOI-induced signaling. These results suggest GPR143 dampens 5-HT2A receptor signaling and weakens behavioral responses to hallucinogens.