Cocaine-induced activation of the proenkephalin system in brain areas and immune cells is reversed by MK-801 pretreatment

ASSIS A; RENNA MS; MONGI BRAGATO B.; BARTOS M; CANCELA L

Estambul

Congreso; The Third Annual International Drug Abuse Research Society/ International Society for Neurochemistry/ESN Satellite Meeting; 2011

IDARS

Drugs of abuse clearly disrupt immune and central functions. We have previously shown that amphetamine influences simultaneously the enkephalinergic system in brain and immune organs, and that met-enkephalin (ENK) would be mediating functional consequences at both levels. The main goal of this study was to determine the influence of an acute cocaine treatment on ENK and proenkephalin (proENK) mRNA levels in mesocorticolimbic brain areas, as well as on a functional parameter of the immune system, the lymphoproliferative response of T-cell populations. The participation of glutamatergic mechanisms in the effects of cocaine at central and immune levels was also studied. Male Wistar rats were injected with an acute dose of cocaine (30mg/Kg ip) or vehicle (VEH), and 4 days after animals were killed. Brain areas and immune organs were obtained and properly processed to measure ENK levels by RIA. Splenic T-cell proliferative response was measured by a mitogenic assay using ConA. In another set of experiments, animals were pre-treated with MK-801 (0.1 mg/kg, i.p.) or VEH, 15 min before cocaine or VEH, and 3 h after the animals were killed and the brain areas and spleen were removed to measure proENK mRNA levels by RT-PCR. Our results demonstrate that cocaine increased ENK and proENK mRNA levels in CNS structures related to drug addiction, such as nucleus accumbens (NAc), and dorsal striatum (ST). MK-801 abrogated cocaine-induced effects on proENK mRNA levels in NAc and ST, similarly to that previously observed following amphetamine. Interestingly, the cocaine-induced decrease in the lymphoproliferative response was found simultaneously to the cocaine-induced changes in brain ENK, as was shown after amphetamine on ENK from either brain areas or immune organs (Assis y col., 2006, 2009, 2011). These findings are discussed in the framework of the role that ENK could be playing in psychostimulant drug addiction and immunosupression like a biochemical bridge that participate at both, central and immune system.