Integrated non-targeted and targeted metabolomics uncovers dynamic metabolic effects during short-term abstinence in methamphetamine self-administering rats

Persistent neurochemical disturbances by repeating drug reward and withdrawal lead to addiction. Particularly, drug withdrawal, usually starting within hours of the last dose, is considered as a critical step in the transition to addiction and a treatment clue. The aim of this study was to uncover metabolic effects associated with methamphetamine (MA) short-term abstinence using both non-targeted and targeted metabolomics. Metabolic alterations were investigated in rat plasma collected immediately after 16 d of MA self-administration (SA) and after 12 and 24 h of abstinence. Principal component analysis revealed that the highest level of separation occurred between the 24-h and saline (control) groups, based on the significantly changed ion features, 257/320/333 and 331/409/388, in the SA/12-h/24-h groups in positive and negative modes of UPLC-QTOF-ESI-MS, respectively. Targeted metabolomics revealed dynamic changes in the biosynthesis/metabolism of amino acids, including the phenylalanine, tyrosine and t...