Metabotropic glutamate receptors are necessary for sensitization by amphetamine

The contribution of metabotropic glutamate receptors (mGluRs) in the ventral tegmental area (VTA) to the induction of locomotor sensitization by amphetamine (AMPH) was investigated. Rats pre-exposed to AMPH in the VTA showed significantly higher locomotor activity when subsequently tested with a systemic AMPH challenge than rats preexposed to VTA saline. Rats pre-exposed to AMPH but co-injected with the selective mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG] did not show this effect. These findings indicate that activation of mGluRs in the VTA is necessary for the induction of locomotor sensitization by AMPH and provide further support for the important role played by excitatory amino acids in this site in the development of sensitization to AMPH.