Methamphetamine-induced decrease in neural glucocorticoid receptors: relationship to monoamine levels.
Methamphetamine (MA) is a potent psychostimulant drug which is neurotoxic to dopamine (DA) and serotonin (5-HT) neurons. It has been previously reported that acute MA administration to adrenalectomized rats produced large dose-related decreases in hippocampal and striatal glucocorticoid receptors (GR). The present study was designed to determine if MA could decrease neural and peripheral GR when administered to adrenal-intact rats using a neurotoxic dosing regimen which produces depletions of brain DA and 5-HT levels. MA (0, 6.25, 12.5 and 25 mg/kg) was administered to adrenal-intact rats every 2 h for a total of 4 doses. Rats were adrenalectomized (ADX) 6 days later and subsequently sacrificed 24 h later. GR and mineralocorticoid receptors (MR) were measured using radioligand binding assays. Tissue levels of 5-HT and DA were measured in order to confirm the neurotoxic effects of MA and also to relate corticosteroid receptor levels to monoamine concentrations. MA produced dose-related decreases in GR levels in the hippocampus, striatum, frontal cortex and hypothalamus. Hippocampal MR were not affected by MA. 5-HT was also decreased in all of these same 4 brain regions, whereas DA was significantly decreased only in the striatum. MA did not decrease GR in cerebellum and similarly had no effect on DA and 5-HT in this region. MA also did not decrease GR or 5-HT levels in the spleen. These results demonstrate that MA produces a decrease in GR in a variety of brain areas, which is related primarily to 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS)
Lowy
M T
MT
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Novotney
S
S
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008221:Lymphoid Tissue / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine