ABSTRACT
Title
Adenosine receptor control of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-induced neurotoxicity and gliosis: differences between adolescent and adult mice
Authors
L. Frau1, A.S. Khairnar 1 and M. Morelli 1,2,3
1 Department of Toxicology, University of Cagliari, 09124 Cagliari , ITALY
2 CNR, Institute of Neuroscience, Cagliari
3 Centre of Excellence for Neurobiology of Dependence
Abstract
Previous studies by our group [1] have shown that caffeine, an adenosine A1/A2A receptor antagonist, potentiated MDMA-induced microglia and astroglia activation in the striatum of mice. Since human use of MDMA is widespread in adults as well as youngster, and is often associated to caffeinated beverages, it is of great importance to evaluate the possible different vulnerability to the effects of MDMA plus caffeine in the younger population. To this scope we studied neurotoxic and neuroinflammatory effects of MDMA plus caffeine in young (30 days) and adult (3 months) C57BL/6J mice. MDMA (4x20 mg/kg) was administered alone or in combination with caffeine (10 mg/kg). Rectal temperature was measured after each administration of MDMA in order to evaluate the role of hyperthermia on MDMA-induced effects. CD11b and GFAP immunoreactivity were evaluated as markers of microglia and astroglia activation in the SNc and striatum, whereas tyrosine hydroxylase (TH) was evaluated in SNc as marker of dopamine neuron degeneration. Results showed that MDMA-induced microglia activation in mice striatum was potentiated by caffeine in adult but not adolescent mice, whereas MDMA-induced astroglia activation was potentiated by caffeine in the striatum of both adults and adolescents mice. In the SNc of adult and adolescent, MDMA did not modify GFAP and increased CD11b, both effects were not influenced by caffeine. Interestingly MDMA-induced decrease in TH positive neurons in the SNc was similar in adolescent and adult mice however, potentiation by caffeine was observed in adolescent but not adults mice. In addition, increase of temperature by MDMA was similar in the two groups and caffeine did not modify it. The abuse of MDMA is a growing worldwide problem; the results of this study suggest that combination of MDMA plus caffeine might have different effects in the adult and adolescent brain.
[1] Khairnar A, Plumitallo A, Frau L, Schintu N, Morelli M. Caffeine enhances astroglia and microglia reactivity induced by 3,4-methylenedioxymethamphetamine ('ecstasy') in mouse brain. Neurotox Res. 2010 May;17(4):435-9..
[1] Khairnar A, Plumitallo A, Frau L, Schintu N, Morelli M. Caffeine enhances astroglia and microglia reactivity induced by 3,4-methylenedioxymethamphetamine ('ecstasy') in mouse brain. Neurotox Res. 2010 May;17(4):435-9..