Table 2.
The role of selected biochemical or physiological effects mediated by hyperthermia that are associated with AMPH and METH neurotoxicity
| Adverse Biochemical or Physiological Effects Associated with Amphetamine or Methamphetamine Neurotoxicity |
|||||||
|---|---|---|---|---|---|---|---|
| Brain Region and Effect | Reactive Oxidative Stress | Elevated Extracellular Glutamate | Hyperactivity of Dopamine Transporter | Blood-Brain Barrier Disruption | Significant Seizure Activity | Meninges and Associated Vasculature | Neuro-inflammation |
| ↓Striatal Dopamine Axons/ Terminals | Strong Supporting Data | Significant Supporting Data | Strong Supporting Data | Not Necessary | Not Necessary | Not Necessary | **Not Necessary? |
| Striatal Neurodegeneration | Supporting Data | Supporting Data | *Indirect | Sparse Supporting Data | Unknown | Not Necessary | Unknown |
| Parietal Neurodegeneration | Supporting Data | Supporting Data | *Indirect | Not Necessary | Not Necessary | Some Supporting Data | Unknown |
| Piriform Neurodegeneration | Some Supporting Data | Indirect Supporting Data | *Indirect | Supporting Data | Supporting Data | Some Supporting Data | Unknown |
| Thalamic Neurodegeneration | Some Supporting Data | Unknown | *Indirect | Supporting Data | Not Necessary | Unknown | Unknown |
| Amygdala Neurodegeneration | Some Supporting Data | Indirect Supporting Data | *Indirect | Supporting Data | Supporting Data | Unknown | Unknown |
| Hippocampal Neurodegeneration | Some Supporting Data | Indirect Supporting Data | *Indirect | Supporting Data | Significant Supporting Data | Unknown | Unknown |
All the adverse biochemical or physiological effects listed are temperature dependent or greatly exacerbated by hyperthermia. The neurotoxicities listed are those that have been characterized histologically. The conclusions shown in the table are opinions of the authors derived from the literature. Most of which are supported to some extent by citation in the text.
Even though systemic immune system activation and peripheral organ damage all precede and correlate very positively with AMPH and METH toxicity, their roles at this point are still being investigated and controversial.
aDopamine plasma membrane (a.k.a. DAT, Slc6a)
*Almost all of the hyperthermic and neurotoxic effects of AMPH and METH are either directly or indirectly due to very high synaptic extracellular levels of dopamine or norepinephrine.
**See text for clarification.