Methamphetamine-induced decrease in neural glucocorticoid receptors: relationship to monoamine levels

Brain Res. 1994 Feb 28;638(1-2):175-81. doi: 10.1016/0006-8993(94)90647-5.

Abstract

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)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenalectomy
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / metabolism
  • Male
  • Methamphetamine / pharmacology*
  • Organ Specificity
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / metabolism*
  • Serotonin / metabolism
  • Spleen / drug effects
  • Spleen / metabolism

Substances

  • Receptors, Glucocorticoid
  • Serotonin
  • Methamphetamine
  • Dopamine