The distinct roles of various neurotransmitters in modulating methamphetamine-induced conditioned place preference in relevant brain regions in mice

Abstract

Objectives Previous studies have shown that methamphetamine (METH) can induce complex adaptive changes in the reward system in the brain, including the changes in the content of neurotransmitters in the signal transduction pathway. However, how the changes of various neurotransmitters in relevant brain reward circuits contribute to METH-induced conditioned place preference (CPP) remains unclear. Methods In this study, first, we designed an animal model of METH-induced CPP. Then we used liquid chromatography-mass spectrometry (LC-MS) to simultaneously determine the contents of various neurotransmitters - dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), glutamic acid (Glu) and glutamine (Gln) - in different brain regions of the prefrontal cortex (PFc), nucleus accumbens (NAc), caudate-putamen (CPu) and hippocampus (Hip), which are believed to be relevant to the drug's reward effect. Results The results of the behavioral experiment suggested that 1.0 mg/kg METH could induce obvious CPP in mice. The results about various neurotransmitters showed that: DA significantly increased in NAc in the METH group; Glu increased significantly in the METH group in PFc and NAc and Gln increased significantly in the METH group in PFc. Conclusions These results suggested that the neurotransmitters of DA, Glu and Gln may work together and play important roles in METH-induced CPP in relevant brain reward circuits, especially in PFc and NAc. These findings therefore could help to advance the comprehensive understanding of the neurochemic and psychopharmacologic properties of METH in reward effect, which is important for future improvements in the treatment of drug addiction.