Sensitization to amphetamine occurs simultaneously at immune level and in met-enkephalin of the nucleus accumbens and spleen: an involved NMDA glutamatergic mechanism.
Administration of psychostimulants can elicit a sensitized response to the stimulating and reinforcing properties 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 inhibitory effect on the splenic T-cell proliferative response, along with an increase in met-enkephalin at limbic and immune levels, 4 days following drug administration. In this study, we evaluated the amphetamine-induced effects at weeks one and three after the same single dose treatment (5 mg/kg, i.p.) on the lymphoproliferative response 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 three weeks, although re-exposure to an amphetamine challenge induced the expression of sensitization to the 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 on the lymphoproliferative response and on met-enkephalin in the NAc and spleen. Furthermore, the NMDA receptor antagonist administered prior to amphetamine challenge also blocked the expression of sensitization in both parameters evaluated. These findings show a long-lasting amphetamine-induced sensitization phenomenon at the immune level in a parallel way to that occurring in the limbic and immune enkephalineric system. A glutamate mechanism is implied in the long-term amphetamine-induced effects at immune level and in the met-enkephalin from NAc and spleen.
Assis
María Amparo
MA
National University of Córdoba, School of Chemical Sciences, Department of Pharmacology, Instituto de Farmacología Experimental de Córdoba-CONICET, Medina Allende y Haya de la Torre, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Hansen
Cristian
C
Lux-Lantos
Victoria
V
Cancela
Liliana Marina
LM
D000661:Amphetamine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004744:Enkephalin, Methionine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004744:Enkephalin, Methionine; D016291:Dizocilpine Maleate; D000661:Amphetamine