Changes in serotonin, dopamine and noradrenaline levels in striatum and nucleus accumbens after repeated administration of the abused drug MDMA in rats.
The selective neurotoxic action of the abused drug 3,4-methylenedioxymethamphetamine (MDMA) on the serotonergic axons ascending from the dorsal raphe nucleus (DRN) is well known. The present study examined the long-term effects of subchronic MDMA treatment on rat brain tissue contents of catecholaminergic neurotransmitters. Two and four weeks after cessation of repeated MDMA treatment (ten consecutive days, 20 mg/kg/day), the tissue neurotransmitter concentrations were measured by means of electrochemical detected HPLC in several forebrain areas and DRN. We found reduced serotonin levels in the whole forebrain at both instants of time. In nucleus accumbens (NAC), the noradrenaline levels were also decreased, whereas dopamine levels were increased 4 weeks after treatment. It is concluded that MDMA causes changes of monoamine transmitter levels outlasting cessation of drug intake for at least 4 weeks. Decreased noradrenaline and/or serotonin may subsequently cause the augmentation of dopamine in NAC, a structure crucially involved in motivation circuits. With exception of transmitter alterations in the NAC, the post drug effects are opposite to the acute effects of MDMA and may underlie the psychiatric changes after MDMA intake in humans.
Mayerhofer
A
A
Zoological Institute, Neuropharmacology, University of Tuebingen, Ob dem Himmelreich 7, 72074 Tuebingen, Germany. andreas.mayerhofer@uni-tuebingen.de
Kovar
K A
KA
Schmidt
W J
WJ
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D006213:Hallucinogens / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D006213:Hallucinogens; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D009638:Norepinephrine