4-HIAA Blocks Methamphetamine-Induced Conditioned Place Preference in Mice Through Modulation of the 5-HT Pathway in...

4-hydroxyindole-3-acetic acid (4-HIAA) is a metabolite of psilocin. Here, we explored the ability of 4-HIAA to cross the blood-brain barrier and its potential effects on methamphetamine (METH)-induced conditioned place preference (CPP) in mice. Treatment with 1-mg/kg 4-HIAA inhibited CPP formation during the acquisition phase, promoted METH extinction and inhibited METH relapse. Furthermore, the regulatory effect of 4-HIAA on METH was underscored by altered 5-HT expression in the nucleus accumbens. Collectively, our findings provide novel insights into the molecular mechanisms of the 4-HIAA-induced blockade of the acquisition, extinction and reinstatement of METH-induced CPP.