Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study

Brain Res. 1980 Jul 7;193(1):153-63. doi: 10.1016/0006-8993(80)90952-x.


Repeated high doses (25 and 100 mg/kg) of methylamphetamine produce long-term depletions of both dopamine (DA) and serotonin (5-HT) in the rat brain. In the DA system, depletions are most pronounced in the neostriatum and substantia nigra, with decreased levels in these two regions being significantly correlated. Within the 5-HT system, levels are most reduced in the amygdala, frontal cortex and neostriatum. When both the DA and 5-HT depleting actions of methylamphetamine are considered, the hypothalamus stands out as one of the more resistant brain regions. The regional pattern of reduced 5-HT levels following methylamphetamine is similar to that seen after p-chloroamphetamine. After both methylamphetamine and p-chloroamphetamine, a loss of 5-HT synaptosomal uptake sites occurs. Serotonergic systems are more sensitive than DA systems to the apparent neurotoxic actions of methylamphetamine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamines / pharmacology*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Serotonin / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism


  • Amphetamines
  • Serotonin
  • Dopamine