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Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine
S F Ali1, G D Newport, R R Holson
1Neurochemistry Laboratory, National Center for Toxicological Research, Jefferson, AR 72079-9502.
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)
Insights
Methamphetamine neurotoxicity is reduced in cold environments. Drugs blocking chloride and glutamate channels also mitigate methamphetamine
Area of Science:
- Neuroscience
- Pharmacology
- Environmental Health
Background:
- Methamphetamine (METH) neurotoxicity is a significant concern.
- Previous research indicated environmental temperature influences METH's effects in rats.
Purpose of the Study:
- To investigate if a cold environment (4°C) or specific ion channel blockers reduce METH-induced neurotoxicity in mice.
- To assess the impact on dopamine (DA) and serotonin (5-HT) levels in the striatum.
Main Methods:
- Adult male CD mice were administered METH (4 x 10 mg/kg or 4 x 20 mg/kg) at either 23°C or 4°C.
- Mice were pretreated with (+)-MK-801, phenobarbital, or diazepam before METH administration at 23°C.
- Striatal levels of DA, DOPAC, HVA, and 5-HT were measured at various time points.
Main Results:
- METH (4 x 10 mg/kg) at 23°C caused an 80% decrease in striatal DA, while at 4°C, the same dose caused only a 20% decrease.
- A higher METH dose (4 x 20 mg/kg) at 4°C resulted in a 54% DA decrease.
- (+)-MK-801 completely blocked METH-induced DA depletion at 23°C, while phenobarbital and diazepam partially blocked it.
- Both cold temperature and the tested drugs blocked METH-induced serotonin depletion.
Conclusions:
- Cold environmental temperature significantly attenuates methamphetamine neurotoxicity in mice.
- Drugs acting on chloride and glutamate ion channels offer neuroprotection against METH-induced dopamine and serotonin depletion.
- These findings suggest potential therapeutic strategies for managing METH toxicity.