Cue-induced Magnetic Resonance Spectroscopy of Glutamate in Addiction Research: Current Evidence, Pros, and Cons

Cues, which induce craving, and may lead to relapse, are an important paradigm for addiction research. Visual cues related to addictive substances trigger powerful neurophysiological responses in the brains of addicts, leading to craving. However, the molecular mechanisms underlying these neurophysiological responses remain incompletely understood. While the role of dopamine in cue-induced phenomena has been extensively studied, the contribution of glutamate, a major excitatory neurotransmitter and a key player in cue-associated phenomena as proposed by animal studies, is less explored in humans. Functional magnetic resonance spectroscopy (fMRS) is a promising tool for investigating glutamatergic modulations in tasks. This review aims to evaluate the potential of fMRS in explaining the dynamics of glutamate during cue-induced phenomena in drug addiction. We discuss the clinical implications, strengths, and limitations of fMRS in this context and propose directions for future research.