Differentially altered mGluR1 and mGluR5 mRNA expression in rat caudate nucleus and nucleus accumbens in the development and expression of behavioralsensitization to repeated amphetamine administration

Altered glutamatergic transmission in the striatum may be implicated in beh avioral sensitization to repeated amphetamine (AMPH) administration. Quanti tative in situ hybridization histochemistry was performed to define the eff ects of acute and chronic AMPH exposures on mRNA expression of Group I meta botropic glutamate receptors (mGluRs) in the striatum. Behavioral ratings i ndicated that the motor activity of rats was significantly higher after the final of five daily AMPH injections (4 mg/kg, i.p.) than that after the fi rst of five. daily AMPH, indicative of the development of behavioral sensit ization. Moreover, the motor activity of rats treated with five daily AMPH was significantly greater than that of rats treated with five daily saline in response to a 2 mg/kg challenge dose of AMPH 7, 14, 28, and 60 days afte r the discontinuation of drug treatments, indicative of the persistent expr ession of behavioral sensitization. Three hours after acute administration of AMPH to naive rats, mGluR1 and mGluR5 mRNA expression in the dorsal (cau datoputamen) and ventral (nucleus accumbens) striatum. showed no change as compared to acute saline injection. In rats that developed behavioral sensi tization to repeated AMPH, mGluR1 levels in the dorsal and ventral striatum were increased by 53% and 43%, respectively, 3 h after the final AMPH trea tment. However, this change did not persist during withdrawal since it was not observed 7, 14, and 28 days after the discontinuation of AMPH treatment . Conversely, mGluR5 levels were markedly reduced 3 h after the final of fi ve daily AMPH treatments in the entire striatum, of sensitized rats (34% an d 77% of controls in the dorsal and ventral striatum, respectively). The re duction persisted at 7, 14, and 28 days of withdrawal. These results reveal a close linkage between striatal Group I mGluR gene expression and behavio ral sensitization to AMPH. This may indicate functional implications of the two subtypes of Group I mGluRs in the regulation of behavioral sensitizati on to the dopamine stimulant. Synapse 41:230-240, 2001. (C) 2001 Wiley-Liss , Inc.