Anales RANF

P.31 INHIBITION OF THE DOPAMINE TRANSPORTER AS AN ANIMAL MODEL OF MANIA MODULATES ADENOSINE RECEPTORS AND INFLAMMATORY RESPONSES IN THE BRAIN M.C.B. Gonçalves 1 , Y. Naaldijk 2,3 , J. Corrêa-Velloso 2,3 , P. Rameshwar 3 , H. Ulrich 2 1 . Federal University of São Paulo, São Paulo, Brazil; 2 . University of São Paulo, São Paulo, Brazil; 3 . New Jersey Medical School, Rutgers University, New Jersey, United States. In this work, we characterized the adenosinergic receptors and enzymes as well as the inflammatory status in an animal model of mania induced by GBR12909 – a selective dopamine transporter inhibitor – as well as the effect of the mood stabilizer lithium carbonate. Young adult C57Bl/6 mice (n = 20) received 12.5 mg/kg GBR 12909 (Sigma Aldrich) I.P. or vehicle (NaCl 0.9%; n = 30) I.P or lithium carbonate in water (Li 2 CO 3 1000 mg/L; n = 5). Prefrontal cortex, hippocampus, striatum and cerebellum were collected and immediately digested or frozen in dry ice and stored in -80°C until further experiments. Gene expression was analyzed by RT-qPCR; nucleotides levels were obtained by luciferase assay; cytokine profile was assessed by protein blotting and data was analyzed in situ with IPA software (Qiagen). Our data show that lithium and GBR12909 effect vary according to the brain region. After GBR12909, adenosine receptors and ectonucleotidases showed significant alterations especially in striatum and cerebellum. Those regions also showed higher levels of pro-inflammatory cytokines and chemokines. ATP, ADP and AMP levels were also affected, but could be reversed by lithium treatment, especially in striatum. Hippocampus didn’t show significant alterations, resembling resilient to both induction of disease and treatment. However, prefrontal cortex, showed high levels of anti- inflammatory cytokines, indicating a possible auto-immune response. Adenosine receptors A2a and A2b and the enzymes CD39 and CD73 seemed to be important targets for further investigation on the adenosinergic effect over neuroinflammatory responses.