Aims: Drug addiction and stress are associated with immunosuppressive states that can influence the vulnerability to a wide variety of diseases, including neoplasia. Repeated as well as an acute exposure to psychostimulants like amphetamine (AMPH) is characterized by enhanced neurochemical and behavioral 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. The main goal of this study was to determine the long-lasting influence of a single dose of AMPH and/or haloperidol (HAL), a nonselective D1/D2 DA receptor antagonist, on stress-induced effects on lymphocyte subpopulations and NK cells. Methods: Male Wistar rats were treated with a single injection of vehicle (VEH) or AMPH (5mg/kg/day IP) on day 1, and exposed to a footshock stress on day 5. Other group was pre-treated with VEH or HAL (1mg/kg IP) 30 min previous AMPH injection. After stress, blood cells were stained with monoclonal antibodies against CD3, CD4, CD8, CD16 and CD45RA and analyzed by multiparameter flow cytometry. Results: The absolute number of peripheral lymphocyte decreased, as well as CD4+ and CD8+ T-cells and B-cells, while NK cells remained unchanged in AMPH-treated rats relative to VEH-treated controls. That immunosuppressive response was abolished by HAL pre-treatment. Conclusions: The present findings complement our previous evidence and are indicative of a modulatory role for DA in the long-lasting 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.
