Regulation of group I metabotropic glutamate receptor expression in the rat striatum and prefrontal cortex in response to amphetamine in vivo

Abstract

G protein-coupled metabotropic glutamate receptors (mGluRs) are expressed in widespread regions of the mammalian brain and are involved in the regulation of a variety of neuronal and synaptic activities. Group I mGluRs (mGluR1 and mGluR5 subtypes) are expressed in striatal medium spiny output neurons and are believed to play an important role in the modulation of cellular responses to dopamine stimulation with psychostimulants. In this study, we investigated the effect of a single dose of the psychostimulant amphetamine on mGluR1/5 protein expression in the rat forebrain in vivo. We found that acute systemic injection of amphetamine at a behaviorally active dose (5 mg/kg) was able to reduce mGluR5 protein levels in a confined biochemical fraction of synaptosomal plasma membranes enriched from the striatum. In contrast to the striatum, amphetamine increased mGluR5 protein levels in the medial prefrontal cortex. These changes in mGluR5 expression in both the striatum and the medial prefrontal cortex were transient and reversible. In addition, protein levels of mGluR1 in the enriched synaptosomal fraction from both the striatum and the medial prefrontal cortex remained stable in response to acute amphetamine. Similarly, Homer1b/c proteins, which are prominent anchoring proteins of mGluR1/5 and are highly expressed in the striatum and the medial prefrontal cortex, showed no change in their protein abundance in striatal and cortical synaptosomes after amphetamine administration. These data demonstrate differential sensitivity of mGluR1 and mGluR5 expression to amphetamine. Acute amphetamine injection is able to alter mGluR5 protein levels at synaptic sites in a subtype- and region-specific manner.