Brain and heart specific alteration of methamphetamine (MAP) distribution in MAP-sensitized rat.
The repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the high accumulation of MAP was observed in the MAP-sensitized animal brain, which suggested that this phenomenon is an important factor in the development or expression of behavioral sensitization. The purpose of the present study is to elucidate the MAP distribution in the MAP-sensitized rat using gas chromatography/mass spectrometry (GC/MS). As a result, the MAP distribution in the heart at 10 min when showing a high accumulation of MAP in the MAP-sensitized rat brain was significantly higher than that of the control rat, whereas no significant differences in the liver, kidney, abdominal muscle, femoral muscle and blood were observed. In the brain and heart, there was no different distribution at 1 min, reflecting only the influx process from blood to brain and heart. On the contrary, there was the significant difference at 10 min, reflecting both the influx and efflux process, suggesting that the efflux process of MAP from brain or heart to blood may be slow due to MAP sensitization. In conclusion, it was clear that the brain and heart specific alteration of the MAP distribution occurred in the MAP sensitization. It was considered that the high accumulation of MAP in the MAP-sensitized rat brain may be related to the expression of behavioral sensitization and that the delayed efflux of MAP in the MAP-sensitized rat heart may be connected with the cardiac toxicity.
Nakagawa
Naoto
N
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Hishinuma
Takanori
T
Nakamura
Hitoshi
H
Yamazaki
Toru
T
Tsukamoto
Hiroki
H
Hiratsuka
Masahiro
M
Ido
Tatsuo
T
Mizugaki
Michinao
M
Terasaki
Tetsuya
T
Goto
Junichi
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000493:pharmacokinetics* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D008694:Methamphetamine