PMID- 21967278 OWN - NLM STAT- MEDLINE DCOM- 20120614 LR - 20131121 IS - 1742-7843 (Electronic) IS - 1742-7835 (Linking) VI - 110 IP - 3 DP - 2012 Mar TI - Dopamine D1 receptor-mediated intracellular responses in the hypothalamus after co-administration of caffeine with MDMA. PG - 283-9 LID - 10.1111/j.1742-7843.2011.00805.x [doi] AB - Markers of dopamine D(1) receptor activation were determined to elucidate intracellular mechanisms associated with the combined effects of caffeine and 3,4 methylenedioxymethamphetamine (MDMA), reported previously to produce increased toxicity, when compared with either drug alone. Caffeine (10 mg/kg) and MDMA (15 mg/kg) were administered to male Sprague Dawley rats alone and in combination. One hour after drug administration, core body temperature and phosphorylation of the dopamine D(1) -related intracellular markers, cAMP response element binding protein (CREB), the dopamine and c-AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and expression of the immediate early gene and cellular activation marker c-fos were determined in the hypothalamus. Co-administration of caffeine with MDMA increased core body temperature when compared with MDMA or caffeine treatment alone. Pre-treatment with the dopamine D(1) receptor antagonist SCH 23390 (1 mg/kg, i.p.), 30 min. prior to caffeine and MDMA administration, produced a hypothermic response to MDMA that was unaffected by caffeine. Co-administration of caffeine with MDMA increased p-CREB, p-DARPP-32 and c-fos expression when compared with either treatment alone. Pre-treatment with SCH-23390 attenuated the changes in p-CREB, p-DARPP and c-fos. The results show an enhanced intracellular response when caffeine is combined with MDMA but not with either agent alone suggestive of synergistic intracellular actions convergent on a dopamine D(1) receptor signalling pathway. A dopamine-related synergy associated with the combined administration of caffeine and MDMA may have important use and safety implications for recreational drug users. CI - (c) 2011 The Authors. Basic & Clinical Pharmacology & Toxicology (c) 2011 Nordic Pharmacological Society. FAU - Vanattou-Saifoudine, Natacha AU - Vanattou-Saifoudine N AD - School of Pharmacy and Pharmaceutical Sciences & Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland. FAU - Behan, Brendan AU - Behan B FAU - Harkin, Andrew AU - Harkin A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111104 PL - England TA - Basic Clin Pharmacol Toxicol JT - Basic & clinical pharmacology & toxicology JID - 101208422 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Receptors, Dopamine D1) RN - 3G6A5W338E (Caffeine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Body Temperature/drug effects MH - Caffeine/administration & dosage/*pharmacology MH - Cyclic AMP Response Element-Binding Protein/genetics/metabolism MH - Dopamine and cAMP-Regulated Phosphoprotein 32/genetics/metabolism MH - Drug Synergism MH - Gene Expression Regulation/drug effects MH - Hypothalamus/drug effects/metabolism MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-fos/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Dopamine D1/*drug effects/metabolism MH - Signal Transduction/drug effects EDAT- 2011/10/05 06:00 MHDA- 2012/06/15 06:00 CRDT- 2011/10/05 06:00 PHST- 2011/10/05 06:00 [entrez] PHST- 2011/10/05 06:00 [pubmed] PHST- 2012/06/15 06:00 [medline] AID - 10.1111/j.1742-7843.2011.00805.x [doi] PST - ppublish SO - Basic Clin Pharmacol Toxicol. 2012 Mar;110(3):283-9. doi: 10.1111/j.1742-7843.2011.00805.x. Epub 2011 Nov 4.