Sensitization to amphetamine occurs simultaneously at immune level and in met-enkephalin of the nucleus accumbens and spleen: An involved NMDA glutamatergic mechanism

MARÍA AMPARO ASSIS; CRISTIAN HANSEN; VICTORIA LUX-LANTOS; LILIANA MARINA CANCELA

BRAIN BEHAVIOR AND IMMUNITY

Elsevier

Lugar: Amstrdam ; Año: 2009 vol. 23 p. 464 - 473

0889-1591

Administration of psychostimulants can elicit a sensitized response to the stimulating and reinforcingproperties of the drugs, although there is scarce information regarding their effects at immune level.We previously demonstrated that an acute exposure to amphetamine (5 mg/kg, i.p.) induced an inhibitoryeffect on the splenic T-cell proliferative response, along with an increase in met-enkephalin at limbicand immune levels, 4 days following drug administration. In this study, we evaluated the amphetamineinducedeffects at weeks one and three after the same single dose treatment (5 mg/kg, i.p.) on the lymphoproliferativeresponse and on the met-enkephalin in the nucleus accumbens (NAc), prefrontal cortex(PfC), spleen and thymus. It was demonstrated that these effects disappeared completely after threeweeks, although re-exposure to an amphetamine challenge induced the expression of sensitization tothe effects of amphetamine on the lymphoproliferative response and on the met-enkephalin from NAc,spleen and thymus, but not in the PfC. Pre-treatment with MK-801 (0.1 mg/kg, i.p.), an N-methyl-D-aspartate(NMDA) glutamatergic receptor antagonist, blocked the effects of a single amphetamine exposure onthe lymphoproliferative response and on met-enkephalin in the NAc and spleen. Furthermore, the NMDAreceptor antagonist administered prior to amphetamine challenge also blocked the expression of sensitizationin both parameters evaluated. These findings show a long-lasting amphetamine-induced sensitizationphenomenon at the immune level in a parallel way to that occurring in the limbic and immuneenkephalineric system. A glutamate mechanism is implied in the long-term amphetamine-inducedeffects at immune level and in the met-enkephalin from NAc and spleen.