Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats

Synapse. 1995 Jan;19(1):56-65. doi: 10.1002/syn.890190108.


The purpose of this study was to compare the effects of amphetamine exposure on subsequent amphetamine-induced changes in behavior and dopamine (DA) release in the dorsal and ventral striatum, as a function of time following the discontinuation of repeated amphetamine treatment. Rats were pretreated with either saline or an escalating-dose amphetamine regimen, and then received a 0.5 mg/kg amphetamine "challenge" after either 3, 7, or 28 days of withdrawal. Animals tested after 28 days of withdrawal were hypersensitive (sensitized) to the locomotor-activating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine-stimulated DA release in both the dorsal and ventral striatum, as revealed by in vivo microdialysis. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine-stimulated DA release. These results establish that time-dependent changes in behavioral sensitization to amphetamine are associated with time-dependent changes in amphetamine-stimulated DA release, and support the hypothesis that persistent sensitization-related changes in striatal DA neurotransmission contribute to the expression of behavioral sensitization.

Publication types

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

MeSH terms

  • Amphetamine / administration & dosage
  • Amphetamine / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiology*
  • Dopamine / physiology*
  • Drug Administration Schedule
  • Male
  • Microdialysis
  • Rats
  • Rats, Inbred Strains
  • Synaptic Transmission / drug effects*
  • Time Factors


  • Amphetamine
  • Dopamine