Behavioral changes and brain energy metabolism dysfunction in rats treated with methamphetamine or dextroamphetamine

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Amphetamines (AMPHs) are known to cause long-term neurotoxicity.
• AMPHs impact dopaminergic, serotoninergic, and glutamatergic brain regions, including the prefrontal cortex, amygdala, hippocampus, and striatum.
• A single AMPH dose induces mitochondrial dysfunction and oxidative stress in rat brains.

Purpose of the Study:

• To investigate the behavioral and energetic effects of dextroamphetamine (d-AMPH) and methamphetamine (m-AMPH) in rats.
• To compare the potency of d-AMPH and m-AMPH on brain function.

Main Methods:

• Rats were administered varying doses of d-AMPH and m-AMPH.
• Behavioral changes, including crossing, rearing, center visits, and sniffing, were recorded.
• Activities of Krebs cycle enzymes and mitochondrial respiratory chain complexes were measured in different brain regions.

Main Results:

• Both d-AMPH and m-AMPH increased crossing and rearing behaviors.
• High-dose m-AMPH (2 mg/kg) increased sniffing behavior, while d-AMPH did not.
• AMPHs significantly decreased Krebs cycle enzyme and mitochondrial respiratory chain complex activities, with region-specific variations.

Conclusions:

• While m-AMPH induced stereotyped sniffing behavior at high doses, d-AMPH did not.
• Both d-AMPH and m-AMPH exhibited similar detrimental effects on the brain's energy metabolism.
• These findings highlight the neurotoxic potential of AMPHs on brain energy pathways.