The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced DA and 5-HT release in the mouse striatum.

A M Górska,K Gołembiowska

doi:10.1007/s12640-014-9501-0

A M Górska, K Gołembiowska

Open Access

https://doi.org/10.1007/s12640-014-9501-0

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Abstract

3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) popular as a designer drug is often used with caffeine to gain a stronger stimulant effect. MDMA induces 5-HT and DA release by interaction with monoamine transporters. Co-administration of caffeine and MDMA may aggravate MDMA-induced toxic effects on DA and 5-HT terminals. In the present study, we determined whether caffeine influences DA and 5-HT release induced by MDMA. We also tried to find out if adenosine A1 and A2A receptors play a role in the effect of caffeine by investigating the effect of the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA and 5-HT release induced by MDMA. Mice were treated with caffeine (10 mg/kg) and MDMA (20 or 40 mg/kg) alone or in combination. DA and 5-HT release in the mouse striatum was measured using in vivo microdialysis. Caffeine exacerbated the effect of MDMA on DA and 5-HT release. DPCPX or KW 6002 co-administered with MDMA had similar influence as caffeine, but KW 6002 was more potent than caffeine or DPCPX. To exclude the contribution of MAO inhibition by caffeine in the caffeine effect on MDMA-induced increase in DA and 5-HT, we also tested the effect of the nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO activity modification. Our findings indicate that adenosine A1 and A2A receptor blockade may account for the caffeine-induced exacerbation of the MDMA effect on DA and 5-HT release and may aggravate MDMA toxicity.

Highlights

3,4-Methylenedioxymethamphetamine (MDMA, ‘‘ecstasy’’) popular as a designer drug is often used with caffeine to gain a stronger stimulant effect
We tried to find out if adenosine A1 and A2A receptors play a role in the effect of caffeine by investigating the effect of the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA and 5-HT release induced by MDMA
The effect of MDMA on 5-HT release was weaker than that on DA release which does not correspond to the rank order of potency for MDMA inhibition of the DA and 5-HT uptake in vitro, where MDMA exhibited a higher potency at serotonin transporter (SERT) than at dopamine transporter (DAT) (Han and Gu 2006)

Summary

Introduction

3,4-Methylenedioxymethamphetamine (MDMA, ‘‘ecstasy’’) is a designer drug structurally related to the hallucinogenic mescaline and amphetamine. The central stimulatory effect of caffeine seems to be related with the blockade of adenosine A1 receptors causing increases of 5-HT, DA and NA turnover (Hadfield and Milio 1989), elevation of DA level in the striatum (Morgan and Vestal 1989). Caffeine co-administered with MDMA potentiated the MDMA effect on extracellular DA level in the striatum of anesthetized rats (Ikeda et al 2011) and enhanced MDMA-induced DA release from the rat striatal slices and this effect was suggested to be mediated via adenosine A1 receptors (Vanattou-Saıfoudine et al 2011). To exclude the contribution of MAO inhibition by caffeine in the caffeine effect on MDMA-induced increase in DA and 5-HT, we tested the effect of the nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO activity modification

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