53. Glutamatergic involvement in amphetamine-induced effects on pulmonary allergic inflammatory response in mice

Abstract

Amphetamine is a drug of abuse that exerts profound effects on behavior, biochemistry and immunity. The aim of this study was to evaluate the involvement of the glutamatergic system in the effects induced by amphetamine in mice OVA-sensitized and challenged by the pretreatment with MK-801, an NMDA glutamate receptor antagonist. In relation to animals treated only with amphetamine we found that pretreatment with MK-801: (1) reverted the decrease in the total leukocytes and in the total number of eosinophils and neutrophils within the bronchoalveolar lavage fluid (BAL) (2) reverted the decrease in the percentage of expression of adhesion molecules l -selectin and ICAM-1 in BAL granulocytes, (3) reverted the decrease in IL-10 and IL-13 in BAL supernatant and (4) reverted the decrease in methacoline-induced tracheal contraction; (5) reverted the degranulation of mast cells in the lungs; (6) did not alter the production of total IgE and IgE-OVA, (7) did not decrease the plasma levels of corticosterone. Taken together, it seems feasible to suggest that the effects induced by amphetamine on lung allergic inflammation requires the participation of the glutamatergic system via NMDA receptors. Possibly, differences in MK-801, amphetamine or MK-801 + amphetamine effects on hypothalamic pituitary adrenal axis and/or sympathetic autonomic nervous system might explain the opposite effects now observed for these drugs given alone or in combination in the pulmonary allergic inflammatory response in mice.