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 el...

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Published inPharmacology, biochemistry and behavior Vol. 44; no. 1; pp. 87 - 98
Main Authors Bowyer, J.F., Gough, B., Slikker, W., Lipe, G.W., Newport, G.D., Holson, R.R.
Format Journal Article
LanguageEnglish
Published New York, NY Elsevier Inc 1993
Elsevier Science
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Summary: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 methampetamine (METH). In 6-month-old rats administered 4 × 5 mg/kg METH at an environmental temperature (ET) of 23°C, peak extracellular DA levels (between 50 and 150 ϱg/10 μl) 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 μl) levels. Increase in 5-HT levles 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°C during dosing decreased the peak and average DA levels attained during the 4 × 5 mg/kg METH administration to about 50% of that observed at a 23°C ET. Increasing the dose to 4 × 10 mg/kg METH (4°C ET) increased peak and average CPU DA levels to 200% that observed during 4 × 5 mg/kg METH at a 23°C ET. However, no significant decreases in total CPU DA content of any rats dosed with METH at a 4°C ET were observed 3 days post-METH. In 12-month-old rats dosed with 4 × 5 mg/kg METH (23°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.
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ISSN:0091-3057
1873-5177
DOI:10.1016/0091-3057(93)90284-Z