Pharmacological and genetic manipulation of glyoxalase-1 (GLO1) does not alter locomotor responses or conditioned place preference induced by cocaine or oxycodone.

Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABAA receptors. MG is metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition of GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking of cocaine-paired cues and ethanol consumption. The goal of these studies was to determine whether manipulation of GLO1 could alter cocaine- or oxycodone-induced locomotor activation and/or conditioned place preference (CPP) to cocaine or oxycodone. We used both pharmacological and genetic manipulations of GLO1 to address this question. Administration of the GLO1 inhibitor s-bromobenzylglutathione cyclopentyl diester (pBBG) did not alter the locomotor response to cocaine or oxycodone. Additionally, pBBG had no significant effect on place preference for cocaine or oxycodone. Genetic knockdown of Glo1, which is conceptually similar to pharmacological inhibition, did not have any significant effects on CPP to cocaine. Finally, Glo1 overexpression did not affect locomotor response to cocaine. In summary, our results did not show any effect of pharmacological or genetic manipulations of GLO1 on the locomotor response or CPP to either cocaine or oxycodone.