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STANKEVICIUS, D. Neuroimmunological aspects of ecstasy (N-methyl-3,4Methylenedioxymethamphetamine – MDMA) on lung inflammatory response in Balb/C mice. 181 p (PhD Thesis on Pharmacology). Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 2010. The N-metil3-4, metilenodioximetanfetamina (MDMA) or ecstasy is a drug widely used amongst young people. This study was undertaken to analyze, under a neuroimmune perspective, the effects of acute MDMA administration on behavioral, neuroendocrine, hematological and immune parameters on Balb/C mice, using for the latter purpose the allergic lung inflammatory response model. It was observed that MDMA produced in mice: 1a differential increase on total locomotion in the different open-field zones; an increase on total locomotion and a decrease on exploratory activity in the hole-board; an increase on both percentage of entrances and time spent on plus-maze open arms; an increase on time spent in the starting box and a decrease of risk assessments in a predator exposition box; 2an increase in corticosterone serum levels; 3an increase in striatal and frontal cortex noradrenaline levels, an increase in striatal dopamine and DOPAC levels, a decrease in cortical DOPAC levels, an increase in striatal 5-HT and 5HIAA levels, a decrease in both 5-HIAA levels and 5-HT turnover rates in hypothalamus and a decrease in striatal and cortical dopamine turnover rates; 4an alteration on leukocyte migration in allergic mice, i.e., decreased percentage of peripheral blood lymphocytes and monocytes, decreased number of granulocytes on bronchoalveolar lavage fluid ( LBA); these effects were reverted by previous RU-486 treatment; 5a decrease in L-selectin expression by monocytes and a tendency towards a decrease in L-selectin expression by lung neutrophils; 6a decrease on expontaneous production of IL-4, IL-5 e IL-10 and IL-4 in LPS-stimulated cultures; 7a decrease in the contraction of allergic mice isolated trachea; and, 8a decrease in bronchial mastocytes degranulation. It was suggested that MDMA-induced anxiety/stress symptoms increasing HHA-axis and/or the autonomic nervous system activities this leading to the immune changes observed presently in the allergic lung inflammation model of asthma used. This model, thus, emerges as a useful tool for the understanding of neuroimmune effects of drugs of abuse. Kay words: Neuroimmunemodulation. Allergic lung inflammation. Bronchoalveolar lavage fluid. Behavior. Corticosterone. Asthma. Cathecolamines. LISTA DE ABREVIATURAS ACTH Hormônio adrenocorticotrópico ADP Adenosina di-fostado AMPH Anfetamina ATP Adenosina trifosfato BDZ Benzodiazepínico BSA Albumina sérica bovina CA Campo aberto Cl Cloro CRF Fator liberador de corticotrofina DA Dopamina DHBA 3,4 diidroxibenzilamina DOPAC Ácido diidroxifenilacético DAG Diacil glicerol DOPAC Ácido 4,4-diidroxifenilacético ERO Espécie reativa de oxigênio GAD Enzima ácido glutâmico descarboxilase GM-CSF Fator estimulador de colônia (granulócito / macrófago) GMP Guanosina cíclica monofosfato HB Hole-Board H2O2 Peróxido de hidrogênio HHA Eixo hipotálamo-hipófise-adrenal HMMA 4-hidroxi-3-metoximetanfetamina HPA Eixo hipotálamo-pituitária-adrenal HVA Ácido homovanílico IL Interleucina IP-3 Fosfatidil inositol-3 LBA Lavado Broncoalveolar LPS Lipopolissacáride LCE Labirinto em cruz elevado MAO Monoaminoxidase MDMA 3,4 metilenodioximetanfetamina MDA metilenodioxianfetamina MDEA metilenodioxietilanfetamina NA Noradrenalina NADPH Diidronicotinamida-adenina-dinucleotídio-fostado NADPH –oxidase Enzima ligada a produção de espécies reativas de oxigênio NMDA Receptor para N-metil-D-aspartato NO Óxido nítrico NOS Enzima óxido nítrico sintetase OVA ovalbumina PBR Receptores benzodiazepínicos periféricos PKC Fosfoquinase – C PMN Células polimorfonucleares PPG Propilenoglicol SI Sistema Imunológico SNAS Sistema Nervoso Autônomo Simpático SNC Sistema Nervoso Central SERT Transportadores de serotonina TNF Fator de necrose tumoral TSH Hormônio tiróide-estimulante 5-HT 5-hidroxitripitamina 5-HIAA Ácido hidroxiindolacético

Aspectos neuroimunológicos do ecstasy (N-metil-3,4-Metilenodioximetanfetamina-MDMA), na inflamação alérgica pulmonar em camundongos Balb/C.