Repeated administration of d-amphetamine facilitates stress-induced immunosuppression: a multiparameter T and B cells analysis by flow cytometry.

MA Assis MS, AM Pacchioni MS, C Collino MS, B Salido-Rentería MS, V Molina PhD, AM Basso PhD, C Sotomayor PhD and L Cancela PhD.

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina

AIMS: Drug addiction and stress are associated with immunosuppression states that altering the vulnerability to a wide variety of diseases, including neoplasia. Repeated exposure to psychostimulants like amphetamine (AMPH) is characterized by enhanced neurochemical and behavioural responses to a subsequent administration of the same drug (sensitization) or to stress (cross-sensitization) involving the activation of central dopaminergic (DA) pathways. We previously demonstrated that chronic AMPH treatment facilitates the immunosuppression following the exposure to an aversive stimulus. This facilitation is reverted by a pre-treatment with haloperidol (HAL), a nonselective D1/D2 DA receptor antagonist. The main goal of this study was to determine the influence of d-amphetamine and/or haloperidol repeated treatment, on stress-induced effects on lymphocyte subpopulations. METHODS: Wistar rats were treated with AMPH (2mg/kg/day IP during 9 days), and subsequently exposed to a footshock stress. Other group was administered with HAL (1mg/kg IP, 30 min previous to each daily AMPH injection). Then, blood cells were stained with monoclonal antibodies against CD3-FITC, CD4-Cy-Chrome, CD8-PE and CD45RA-Cy-Crhome and were analyzed by multiparameter flow cytometry. RESULTS: The absolute number of peripheral lymphocyte decreased, as well as CD4+ and CD8+ T-cells and B-cells in chronically AMPH-pretreated rats relative to vehicle-treated controls. That immunosuppressive response was abolished by HAL administration. CONCLUSIONS: The present findings complement our previous evidence and are indicative of a modulatory role for DA in the facilitating process induced by AMPH on stress-induced immunosuppressive effects. Considering that drugs of abuse, stress, and psychiatric disorders are associated with deficits in the immune system, this study might contribute to understand the abnormal immunologic function frequently observed in human addicts.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Carcinogenesis.