Serum proteomic analysis during nicotine self-administration, extinction and relapse in rats

Nicotine dependence is known to induce long-term neural adaptations in brain. The purpose of this study was to verify whether specific protein patterns related to nicotine self-administration states could also be detected in a peripheral tissue. A serum proteomic analysis was performed by 2D electrophoresis on samples taken at six time-points: N, Naïve; P, Priming; S, Self-administration; W, Withdrawal; E, Extinction; R, Relapse. After image analysis, spot volume values were submitted to a Principal Component Analysis and relevant comparisons were selected. In N versus S; S versus W; E versus R; S versus R; and S versus E comparisons a clear separation between groups could be observed, suggesting that each self-administration state correlates with a specific protein expression pattern. Partial least squares-discriminant analysis was adopted to rank proteins by the contribution to the overall separation. A number of spots were identified; among them, C reactive protein and hemopexin displayed a significant reduction after nicotine administration; two hemopexin isoforms were decreased in the S state and antithrombin III was increased in the E phase. This study showed that specific protein patterns related to the nicotine self-administration states exist in serum. Further development of this approach may provide biomarkers to assess dependence states of drug-taking individuals.