Chronic and acute effects of 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') administration on the dynorphinergic system in the rat brain.
The prodynorphin system is implicated in the neurochemical mechanism of psychostimulants. Exposure to different drugs of abuse can induce neuroadaptations in the brain and affect opioid gene expression. The present study aims to examine the possibility of a common neurobiological substrate in drug addiction processes. We studied the effects of single and repeated 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') on the gene expression of the opioid precursor prodynorphin, and on the levels of peptide dynorphin A in the rat brain. Acute (8 mg/kg, intraperitoneally) 3,4-methylenedioxy-N-methylamphetamine markedly raised, two hours later, prodynorphin mRNA levels in the prefrontal cortex, and in the caudate putamen, whereas it decreased gene expression in the ventral tegmental area. Chronic (8 mg/kg, intraperitoneally, twice a day for 7 days) 3,4-methylenedioxy-N-methylamphetamine increased prodynorphin mRNA in the nucleus accumbens, hypothalamus and caudate putamen and decreased it in the ventral tegmental area. Dynorphin A levels increased after chronic treatment in the ventral tegmental area and decreased after acute treatment in the nucleus accumbens, prefrontal cortex and hypothalamus. These findings confirm the role of the dynorphinergic system in mediating the effects of drugs of abuse, such as 3,4-methylenedioxy-N-methylamphetamine, in various regions of the rat brain, which may be important sites for the opioidergic mechanisms activated by addictive drugs.
Di Benedetto
M
M
Department of Pharmacology, University of Bologna, Irnerio 48, 40126 Bologna, Italy.
D'addario
C
C
Candeletti
S
S
Romualdi
P
P
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects*; D004399:Dynorphins / Q000187:drug effects* / Q000378:metabolism; D004745:Enkephalins / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004745:Enkephalins; D006213:Hallucinogens; D011498:Protein Precursors; D012333:RNA, Messenger; D004399:Dynorphins; C033660:preproenkephalin; D018817:N-Methyl-3,4-methylenedioxyamphetamine