Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine

Synapse. 1996 Mar;22(3):217-25. doi: 10.1002/(SICI)1098-2396(199603)22:3<217::AID-SYN3>3.0.CO;2-F.


Methamphetamine (m-AMPH) treatment produces long-lasting damage to striatal and cortical monoaminergic terminals and may also injure nonmonoaminergic cortical neurons. Evidence suggests that both dopamine (DA) and glutamate (GLU) play crucial roles in producing this damage. We used quantitative autoradiography to examine [3H]mazindol ([3H]MAZ) binding to striatal DA transporters and [3H]GLU binding to N-methyl-D-aspartate (NMDA) receptors in the striatum and cortex 1 week and 1 month after a neurotoxic regimen of m-AMPH. Rats received m-AMPH (4 mg/kg) or saline (SAL) (1 ml/kg) in four s.c. injections separated by 2 h intervals. One week after m-AMPH, the ventral and lateral sectors of the striatum showed the greatest decreases in both [3H]MAZ and [3H]GLU binding, while the nucleus accumbens (NA) showed no significant decreases. One month after m-AMPH, striatal [3H]MAZ binding was still significantly decreased, while NMDA receptor binding had recovered. Surprisingly, the parietal cortex showed a m-AMPH-induced increase in NMDA receptor binding in layers II/III and IV 1 week after m-AMPH and only in layers II/III 1 month after m-AMPH. The prefrontal cortex showed no m-AMPH-induced changes in NMDA receptor binding at either time point. This is the first demonstration that a regimen of m-AMPH that results in long-lasting damage to DA terminals can alter forebrain NMDA receptor binding. Thus, repeated m-AMPH treatments may produce changes in glutamatergic transmission in selected striatal and cortical regions.

Publication types

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

MeSH terms

  • Animals
  • Autoradiography
  • Carrier Proteins / metabolism
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Dopamine Agents / toxicity*
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / metabolism
  • Glutamic Acid / metabolism
  • Image Processing, Computer-Assisted
  • Male
  • Mazindol / metabolism
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Methamphetamine / toxicity*
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Nerve Tissue Proteins*
  • Nervous System Diseases / chemically induced
  • Nervous System Diseases / metabolism*
  • Nervous System Diseases / pathology
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Carrier Proteins
  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Methamphetamine
  • Mazindol