A simple behavioral test in mice may help regulators quickly identify new hallucinogenic drugs. Mice given the hallucinogen-like compound DOI showed aversive effects in a conditioned place aversion test and abnormal behavior in a marble-burying test. These responses likely stem from the drug's hallucinogenic properties. The findings suggest that such rodent tests could serve as a rapid, accurate screening method for designating new psychoactive substances as controlled drugs, aiding prevention of drug abuse.
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.