3,4-Methylenedioxymethamphetamine (MDMA), but not morphine, alters APP processing in the rat brain.
The abuse of drugs such as opioids and 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') can have detrimental effects on the cognitive functions, but the exact molecular mechanism whereby these drugs promote neurodegeneration remains to be elucidated. The major purpose of the present pilot study was to determine whether the chronic in-vivo administration of morphine (10 mg/kg) or MDMA (1 mg/kg) to rats can alter the expression and processing of amyloid precursor protein (APP), the central molecule in the proposed pathomechanism of Alzheimer's disease. MDMA treatment significantly decreased the production of APP in the cytosolic fraction of the brain cortex. A concomitant 25% increase was found both in the beta-secretase (BACE) and APP mRNA levels (108%). In contrast, in the applied single dosage chronic morphine treatment did not influence either the APP and BACE protein levels or the APP mRNA production. These results indicate that the chronic use of 'ecstasy', but not morphine, may be harmful via a novel mode of action, i.e. by altering the APP expression and processing in the brain.
Department of Psychiatry and Alzheimer's Disease Research Centre, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary. kalmanj@nepsy.szote.u-szeged.hu
János
J
Kálmán
Annamária
A
Bjelik
Marietta
M
Hugyecz
Júlia
J
Tímár
Zsuzsanna
Z
Gyarmati
Marianna
M
Zana
Zsuzsanna
Z
Fürst
Zoltán
Z
Janka
Zoltán
Z
Rakonczay
Zoltán
Z
Horváth
Magdolna
M
Pákáski
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018490:Serotonin Agents / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D000701:Analgesics, Opioid; D012333:RNA, Messenger; D018490:Serotonin Agents; D009020:Morphine; D053829:Amyloid Precursor Protein Secretases; D018817:N-Methyl-3,4-methylenedioxyamphetamine