Abstract
INTRODUCTION: It is well known that opiate addiction is a neurobiological disease associated with dysregulation of multiple neurotransmitters and neurochemicals. Previous ex-vivo (1)H nuclear magnetic resonance (NMR) studies have yielded mixed findings concerning opiate-induced neurometabolic changes at key reward-addiction sites. Whether such changes reflect the conditions in a live animal remains unknown. The present study was therefore designed to fill this knowledge gap by determining the effects of morphine-induced neurometabolic changes under in-vivo conditions. METHODS: In-vivo (1)H NMR spectroscopy (SA Instruments, Stony Brook, NY) was used to measure neurochemical changes in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of mice, subjected to twice-daily injections of morphine (10 mg kg(-1) s.c.) for five days. RESULTS: Morphine induced significant changes in the concentrations of a number of metabolites in both mPFC and NAc. The glutamine component of the glutamine-glutamate-GABA excitatory-inhibitory cycle, increased in both mPFC and NAc. Significant increase in glutamate was also observed at mPFC, but not in NAc. The phosphocreatine, marker for energy metabolism, and the N-acetylaspartate marker for neuronal viability and energy metabolism decreased significantly in both mPFC and NAc. Glycerophosphocholine + phosphocholine, markers for cell membrane integrity, increased significantly in both NAc and mPFC after morphine. The antioxidant neurometabolites taurine and glutathione increased significantly in NAc; however, taurine decreased, and glutathione was unchanged in mPFC after morphine. Inositol, a marker for neuroinflammation, increased significantly in NAc. CONCLUSION: The present study is the first in-vivo (1)H NMR spectroscopy in mice to demonstrate morphine-induced dysregulation of multiple metabolites and neurochemicals within the reward-addiction neurocircuitry.