Nicotine is the main substance responsible for the development of tobacco addiction. The α3β4 nicotinic acetylcholine receptors (nAChRs) are a potential key target for mitigating nicotine reward. Preliminary studies in our laboratory suggest that α-conotoxin S9KTxID serves as a selective and potent antagonist targeting α3β4 nAChRs, which may be beneficial in addressing nicotine addiction. However, the mechanisms of S9KTxID treatment in nicotine addiction are still to be determined. This study aimed to identify the differential metabolic profiles of S9KTxID treatment in nicotine addiction using an untargeted metabolomic profiling method. As demonstrated by behavioral experiments, S9KTxID effectively attenuated nicotine-induced conditioned place preference (CPP) expression without exerting inhibitory effects on the central nervous system (CNS). The results of untargeted metabolomics revealed that eight metabolites were significantly altered after S9KTxID treatment, particularly phenylalanine. S9KTxID also attenuated nicotine-induced metabolic disorders by regulating phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, our findings suggest that S9KTxID could be a potential therapeutic compound for nicotine addiction.
Wang et al. (Thu,) studied this question.
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