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

The expression of glutamate receptor/subunit mRNAs was examined 3 weeks aft er 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 sit u hybridization and RT-PCR. In nucleus accumbens, acute cocaine treatment s ignificantly reduced the mRNA level for GluR3, GluR4, and NMDAR1 subunits, whereas repeated cocaine reduced the level for GluR3 mRNA. Acute cocaine tr eatment also reduced the NMDAR1 mRNA level in dorsolateral striatum and Ven tral tegmental area. In prefrontal cortex, repeated cocaine treatment signi ficantly increased the level of GluR2 mRNA, The GluR2 mRNA level was not ch anged by acute or repeated cocaine in any other brain regions examined. Rep eated 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 transmi ssion and the response to stimulation of ionotropic receptors. Thus, the ob served changes in levels of AMPA and NMDA receptor subunits and the mGluR5 metabotropic receptor may alter excitatory neurotransmission in the mesocor ticolimbic dopamine system, which could play a significant role in the endu ring biochemical and behavioral effects of cocaine.