Effects of a cold environment or age on methamphetamine-induced dopamine release in the caudate putamen of female rats.
Extracellular levels of dopamine (DA) and metabolites as well as serotonin [5-hydroxytryptamine (5-HT)] and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the caudate putamen (CPU) of either 6- or 12-month-old female rats using microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) before, during, and after four consecutive injections (given at 2-h intervals) of methamphetamine (METH). In 6-month-old rats administered 4 x 5 mg/kg METH at an environmental temperature (ET) of 23 degrees C, peak extracellular DA levels (between 50 and 150 rho g/10 microliters) were attained 30-45 min after each dose of METH while dihydroxyphenylacetic acid (DOPAC) decreased steadily after the first doses of METH until it reached a plateau at 50% of control (550-700 pg/10 microliters) levels. Increases in 5-HT levels during METH administrations paralleled DA increases while 5-HIAA decreases paralleled DOPAC decreases. The total CPU DA and 5-HT content of these rats was about 65% of control at 3 days post-METH. Reducing the ET to 4 degrees C during dosing decreased the peak and average DA levels attained during the 4 x 5 mg/kg METH administration to about 50% of that observed at a 23 degrees C ET. Increasing the dose to 4 x 10 mg/kg METH (4 degrees C ET) increased peak and average CPU DA levels to 200% that observed during 4 x 5 mg/kg METH at a 23 degrees C ET. However, no significant decreases in total CPU DA content of any rats dosed with METH at a 4 degrees C ET were observed 3 days post-METH. In 12-month-old rats dosed with 4 x 5 mg/kg METH (23 degrees C ET), the peak and average extracellular DA levels were only 30-60% that of 6-month-old rats. However, the CPU DA content of older rats was significantly decreased both 3 (30% control) and 14 (60% control) days post-METH. In summary, METH toxicity may not be predicted solely by the extracellular levels of DA attained during METH administration; age and ET also greatly influence METH neurotoxicity.
Bowyer
J F
JF
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Gough
B
B
Slikker
W
W
Lipe
G W
GW
Newport
G D
GD
Holson
R R
RR
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003080:Cold Temperature; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013654:Taurine / Q000378:metabolism
D015306:Biogenic Monoamines; D005971:Glutamates; D015102:3,4-Dihydroxyphenylacetic Acid; D013654:Taurine; D012701:Serotonin; D018698:Glutamic Acid; D008694:Methamphetamine; D004298:Dopamine