Group II Metabotropic and -Amino-3-hydroxy-5-methyl-4- isoxazole Propionate (AMPA)/Kainate Glutamate Receptors Regulate the Deficit in Brain Reward Function Associated with Nicotine Withdrawal in Rats

This study investigated the role of ionotropic and metabotropic glutamate receptors in the deficits in brain reward function, as measured by elevations in intracranial self-stimulation (ICSS) re-ward thresholds, associated with nicotine withdrawal. The group II metabotropic glutamate (mGluII) receptor agonist LY314582 [a racemic mixture of LY354740 ([]-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid])] (2.5–7.5 mg/kg) precipitated withdrawal-like elevations in ICSS thresholds, a sensitive measure of reward function, in nicotine-dependent but not control rats. LY314582 did not affect response latencies, a measure of performance in the ICSS paradigm. Bilateral microinfusion of LY314582 (10–100 ng/ side) into the ventral tegmental area likewise precipitated dose-dependent threshold elevations in nicotine-dependent rats. Fur-thermore, a single injection of the mGluII receptor antagonis