Positive allosteric modulator of GLT-1 reduces methamphetamine hyperlocomotion, sensitization and conditioned place preference in mice.

Abstract

NA-014 is a positive allosteric modulator (PAM) of glutamate transporter subtype 1 (GLT-1) that increases glutamate reuptake. Since enhanced glutamate transmission facilitates methamphetamine (METH) hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP), we hypothesized that NA-014 (60 mg/kg) would reduce these effects in male mice. NA-014 reduced acute ambulation induced by METH and behavioral sensitization during repeated METH. NA-014 given after METH conditioning reduced expression of METH CPP. NA-014 injected during METH conditioning did not affect development of METH CPP, and NA-014 did not affect spatial memory. These results suggest that GLT-1 PAMs reduce METH-induced behavioral effects in mice.