Neuroadaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment

J Neurochem. 1999 Jan;72(1):157-65. doi: 10.1046/j.1471-4159.1999.0720157.x.

Abstract

The expression of glutamate receptor/subunit mRNAs was examined 3 weeks after discontinuing 1 week of daily injections of saline or cocaine. The level of mRNA for GluR1-4, NMDAR1, and mGluR5 receptors was measured with in situ hybridization and RT-PCR. In nucleus accumbens, acute cocaine treatment significantly reduced the mRNA level for GluR3, GluR4, and NMDAR1 subunits, whereas repeated cocaine reduced the level for GluR3 mRNA. Acute cocaine treatment also reduced the NMDAR1 mRNA level in dorsolateral striatum and ventral tegmental area. In prefrontal cortex, repeated cocaine treatment significantly increased the level of GluR2 mRNA. The GluR2 mRNA level was not changed by acute or repeated cocaine in any other brain regions examined. Repeated cocaine treatment also significantly increased mGluR5 mRNA levels in nucleus accumbens shell and dorsolateral striatum. Functional properties of the ionotropic glutamate receptors are determined by subunit composition. In addition, metabotropic glutamate receptors can modulate synaptic transmission and the response to stimulation of ionotropic receptors. Thus, the observed changes in levels of AMPA and NMDA receptor subunits and the mGluR5 metabotropic receptor may alter excitatory neurotransmission in the mesocorticolimbic dopamine system, which could play a significant role in the enduring biochemical and behavioral effects of cocaine.

Publication types

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

MeSH terms

  • Adaptation, Physiological / physiology
  • Animals
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology*
  • Corpus Striatum / chemistry
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology
  • Dopamine Uptake Inhibitors / pharmacology*
  • Gene Expression / drug effects
  • Glutamic Acid / metabolism
  • Male
  • Molecular Sequence Data
  • Nucleus Accumbens / chemistry
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology
  • Prefrontal Cortex / chemistry
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / genetics*
  • Receptors, Kainic Acid / genetics*
  • Receptors, Metabotropic Glutamate / genetics*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Ventral Tegmental Area / chemistry
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology

Substances

  • Dopamine Uptake Inhibitors
  • Gluk1 kainate receptor
  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • glutamate receptor ionotropic, AMPA 3
  • glutamate receptor ionotropic, AMPA 4
  • Glutamic Acid
  • Cocaine
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1

Associated data

  • GENBANK/D10891
  • GENBANK/M38060
  • GENBANK/M38061
  • GENBANK/M38062
  • GENBANK/M38063
  • GENBANK/X63255