The broad goal of the proposed studies is to determine the effect of morphine on the generation and expression of immunity to the protozoan parasite, Toxoplasma gondii, a major opportunistic pathogen of the CNS in AIDS patients. The work will focus on the impact of morphine in three physiologically pertinent experimental models of Toxoplasma infection: (i) chronic primary CNS infection, (11) a vaccination model, and (iii) exposure to morphine in utero. We will examine the effect of morphine on parameters of immune resistance in mice chronically infected with an ordinarily avirulent strain of T. gondil. Lymphocytes in peripheral blood, spleen, and the brain of morphine-treated and untreated mice with or without established chronic infections will be analyzed with regard to numbers, expression of markers of activation, and capacity to produce relevant cytokines and chemokines. We will also determine the effect of morphine on the generation and expression of immunity in mice given a Toxoplasma vaccine. Morphine-treated or untreated mice will be vaccinated with an avirulent strain of T. gondii, and the quality of their subsequent acquired immunity evaluated. In other experiments, mice will first be vaccinated then treated later with morphine to evaluate the effect of morphine on the expression of immunity that has already been generated. Finally, we will determine the effect of morphine on the development of immunity in mice exposed to morphine in utero. Pregnant mice will be treated with morphine and the immunological development and functional capabilities of their offspring evaluated postnatally and as adults in the context of anti-Toxoplasma immunity. Together, these studies will provide a comprehensive immunological foundation upon which to build detailed further analyses of the effects of an opioid drug on immunity to opportunistic infection.
| Li, M D; van der Vaart, A D (2011) MicroRNAs in addiction: adaptation's middlemen? Mol Psychiatry 16:1159-68 |
