Low Environmental Temperatures or Pharmacologic Agents That Produce Hypothermia Decrease Methamphetamine Neurotoxicity in Mice

Brain Res. 1994 Sep 26;658(1-2):33-8. doi: 10.1016/s0006-8993(09)90007-5.

Abstract

Recently we have reported that methamphetamine (METH) neurotoxicity in rats depends on the environmental temperature. Here, we evaluate whether a cold environment (4 degrees C) or drugs which chloride and glutamate ion channel function block METH neurotoxicity in mice. Adult male CD mice received METH i.p. (4 x 10 mg/kg METH at 23 degrees C along with saline. 2.5 mg/kg (+)-MK-801, 40 mg/kg phenobarbital or 2.5 mg/kg diazepam and either 4 x 10 or 4 x 20 mg/kg METH at 4 degrees C). Multiple injections of METH (4 x 10 mg/kg i.p.) at room temperature (23 degrees C) produced a significant depletion of dopamine (DA) in striatum at 24, 72 h, 1 and 2 weeks. Three days post 4 x 10 mg/kg METH at 23 degrees C, an 80% decrease in striatal dopamine (DA) occurred while the same dose at 4 degrees C produced only a 20% DA decrease, and 4 x 20 mg/kg METH at 4 degrees C produced a 54% DA decrease. At 23 degrees C (+)MK-801 completely blocked while phenobarbital (40% decrease) and diazepam (65% decrease) partially blocked decreases in striatal DA produced by 4 x 10 mg/kg METH. Decreases in DOPAC and HVA were similar to the decreases in DA after METH and antagonists. Multiple injections of METH (4 x 10 mg/kg, i.p.) at room temperature also produced a significant depletion of serotonin (5-HT) in striatum at 24, 72 h, 1 and 2 weeks. This depletion of 5-HT at room temperature was blocked either by changing the environmental temperature to 4 degrees C, or by pretreatment with MK-801, diazepam and phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology*
  • Chloride Channels / drug effects
  • Cold Temperature*
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism
  • Environmental Exposure*
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Methamphetamine / antagonists & inhibitors
  • Methamphetamine / toxicity*
  • Mice
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Serotonin / metabolism

Substances

  • Chloride Channels
  • Receptors, N-Methyl-D-Aspartate
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Methamphetamine
  • Hydroxyindoleacetic Acid
  • Dizocilpine Maleate
  • Dopamine
  • Homovanillic Acid