A rat's brain, on and off methamphetamine

Methamphetamine is a highly addictive stimulant that increases the activity of neurotransmitters, particularly dopamine, in the brain. Scientists lack a detailed understanding of the neurochemical changes that occur during methamphetamine use and withdrawal, which could help them develop new treatments or diagnostic tests for addiction. So, Chul-Ho Jeong, Sooyeun Lee and colleagues wanted to investigate metabolic alterations in the early withdrawal period following methamphetamine self-administration in rats.

The researchers trained rats to give themselves infusions of methamphetamine or saline (as a control) upon pressing a lever. After 16 days, the team removed rats' access to the drug and collected blood samples at 0, 12 and 24 hours after withdrawal. The researchers found substantial changes in metabolic pathways related to energy metabolism, the nervous system and cell membrane lipid metabolism. For example, the amino acids phenylalanine, tyrosine and tryptophan -- which are precursors of several neurotransmitters -- were depleted in methamphetamine-using rats compared with controls, but during withdrawal, the levels recovered. These and other potential biomarkers could help identify early warning signs of methamphetamine dependence, the researchers say.