The effect of cocaine sensitization on mouse immunoreactivity.

Recent studies indicate a role of the immune system in the behavioral effects of cocaine in rodents. In the present study, we attempted to find a correlation between the behavioral changes induced by repeated, intermittent administration of cocaine and some immunological consequences of sensitization to cocaine. Male Albino Swiss mice were treated repeatedly (for 5 days) with cocaine (10 or 15 mg/kg, intraperitoneally, ip). On day 9, they received a challenge dose of cocaine (10 or 15 mg/kg). Acute administration of cocaine increased the locomotor activity of mice. In animals treated repeatedly with the higher dose of cocaine, the locomotor hyperactivity induced by a challenge dose of the psychostimulant (15 mg/kg) was ca. twice as high as that after its first administration; in consequence, evidence for behavioral sensitization was obtained. Immune functions were evaluated by measuring the ability of splenocytes to proliferate and to produce cytokines such as interferon-gamma (IFN-gamma), interleukin (IL)-4 and IL-10. Acute cocaine administration significantly decreased proliferation of splenocytes to concanavalin A (Con A) and increased their ability to produce IFN-gamma. Repeated intermittent treatment with cocaine in a dose of 10 mg/kg significantly decreased the thymus weight and the proliferative response of T cells to a suboptimal dose of Con A. Sensitization with the higher dose of cocaine significantly enhanced IFN-gamma production. These data indicate that cocaine sensitization results in the development of a tolerant state to the cocaine-induced suppression of a thymus dependent T-lymphocyte response. It may be suggested that the cocaine sensitization partly depends on the altered balance of cytokine production, e.g. an increase in IFN-gamma production. Since repeated, intermittent use of cocaine by humans leads to psychoses or craving for this drug, our findings also seem to indicate considerable importance of monitoring and correcting immune changes in the therapy of cocaine addiction.