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Related Experiment Videos

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

M T Lowy1, S Novotney

  • 1Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.

Brain Research
|February 28, 1994
PubMed
Summary
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Methamphetamine (MA) neurotoxicity decreases brain glucocorticoid receptors (GR) in adrenal-intact rats, primarily linked to serotonin (5-HT) depletions. Dopamine (DA) levels were also affected in specific brain regions.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Endocrinology

Background:

  • Methamphetamine (MA) is a neurotoxic psychostimulant affecting dopamine (DA) and serotonin (5-HT) neurons.
  • Previous studies indicated MA decreases glucocorticoid receptors (GR) in adrenalectomized rats.
  • The impact of MA on GR in adrenal-intact individuals requires further investigation.

Purpose of the Study:

  • To investigate if MA administration to adrenal-intact rats decreases neural and peripheral GR.
  • To correlate MA-induced changes in GR with depletions in brain DA and 5-HT levels.
  • To examine the effect of MA on mineralocorticoid receptors (MR).

Main Methods:

  • Adrenal-intact rats received escalating doses of MA (0-25 mg/kg) every 2 hours for 4 doses.
  • Rats were adrenalectomized (ADX) 6 days post-MA and sacrificed 24 hours later.

Related Experiment Videos

  • Glucocorticoid receptors (GR), mineralocorticoid receptors (MR), DA, and 5-HT levels were quantified using radioligand binding assays and tissue concentration measurements.

    • Main Results:

    • MA caused dose-dependent reductions in GR levels in the hippocampus, striatum, frontal cortex, and hypothalamus.
    • Serotonin (5-HT) levels were decreased in the same brain regions affected by MA.
    • Dopamine (DA) was significantly reduced only in the striatum; hippocampal MR and peripheral GR/5-HT remained unaffected.

    Conclusions:

    • Methamphetamine administration induces dose-related decreases in brain GR, particularly in regions rich in serotonin.
    • The observed reduction in GR appears primarily associated with MA-induced serotonin depletions rather than dopamine.
    • These findings highlight the complex neurochemical interactions of MA and its impact on corticosteroid receptor regulation.