Distinct metabolite profiles induced by alcohol and nicotine exposure in zebrafish: Implications for understanding shared dopaminergic pathways in addiction

Addiction to alcohol and nicotine, whether individually or in combination, represents a significant global health challenge. These substances are known to activate a shared final neuronal pathway within the dopaminergic system, which is crucial for mediating the pleasurable sensations associated with reward. To explore whether the brain metabolite profile of individuals with addiction could elucidate the mechanisms underlying this common neuronal pathway, we conducted a comprehensive analysis of the metabolite profiles from zebrafish brains exposed to alcohol, nicotine, and their combination under rigorously controlled experimental conditions. Our findings reveal that each addictive substance generates a distinct 1H NMR metabolite profile. Specifically, alcohol exposure was associated with a marked increase in taurine levels and a decrease in N-acetyl L-aspartate (NAA) levels, correlating with alcohol's antagonistic effects on excitatory neurotransmission and a decline in overall brain health. Conversely, nicotine exposure resulted in an increase in NAA and levels of common neurotransmitters, aligning with previous studies that highlight nicotine's role in enhancing excitatory neurotransmission, memory formation, and neuroprotection. Notably, our investigation did not identify a shared metabolite that could elucidate the mechanisms of the drug-induced common neuronal pathway. These results underscore the complexity of the metabolic alterations induced by alcohol and nicotine and suggest that distinct pathways may be activated by each substance, warranting further investigation into their individual and combined effects on brain metabolism and function.