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Related Experiment Videos

Cocaine. Selective regional effects on central monoamines

M G Hadfield1

  • 1Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

Molecular Neurobiology
|August 1, 1995
PubMed
Summary

Cocaine significantly alters serotonin, norepinephrine, and dopamine levels across multiple mouse brain regions, with the amygdala showing the most comprehensive changes in neurotransmitter utilization.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Cocaine is a potent psychostimulant with known effects on monoamine neurotransmitters.
  • Understanding cocaine's impact on specific brain regions is crucial for elucidating its neurobiological mechanisms.

Purpose of the Study:

  • To investigate the dose-dependent effects of cocaine hydrochloride on neurotransmitter concentrations and utilization in nine distinct brain regions of adult male ICR mice.
  • To identify brain regions and neurotransmitter systems most sensitive to acute cocaine administration.

Main Methods:

  • Adult male ICR mice were administered cocaine hydrochloride (0, 10, or 50 mg/kg) intraperitoneally.
  • Brain tissues from nine regions were isolated 30 minutes post-injection.
  • High-performance liquid chromatography (HPLC) was used to quantify norepinephrine, dopamine, serotonin, and their metabolites.

Main Results:

  • Serotonergic systems showed dramatic, dose-dependent decreases in 5-hydroxyindoleacetic acid/serotonin (5HIAA/5-HT) ratios across most brain regions, particularly the amygdala, prefrontal cortex, hypothalamus, and thalamus.
  • Noradrenergic systems were affected in the amygdala, prefrontal cortex, and hypothalamus at lower doses.
  • Dopaminergic responses were complex, with varied changes in DOPAC/DA, HVA/DA, and 3MT/DA ratios across regions and doses, with the amygdala exhibiting the most widespread alterations.

Conclusions:

  • Cocaine profoundly impacts monoamine systems in the mouse brain, with serotonergic pathways being highly sensitive.
  • The amygdala is a key region demonstrating comprehensive cocaine-induced changes across all three major monoamine systems.
  • Neurotransmitter metabolite/neurotransmitter ratios serve as effective indicators of cocaine's dose-dependent effects on neurotransmitter utilization in specific brain nuclei.

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