Blockade of mGLUR5 receptors differentially alters amphetamine-induced enhancement of locomotor activity and of brain stimulation reward.

This study was aimed at determining the role of mGLUR5 glutamate receptors on amphetamine-induced enhancement of locomotion and of brain stimulation reward (BSR). The effect of different doses of the mGLUR5 antagonist, MPEP (0, 1, 3 and 9 mg/kg, i.p.), was assessed on reward induced by electrical stimulation of the lateral hypothalamus, and on the enhancement of reward by amphetamine (1 mg/kg, i.p.) in adult male Long Evans rats. The effect of a single dose of MPEP (0 and 9 mg/kg) on amphetamine-induced increase in locomotor activity was also assessed. Systemic injection of MPEP alone did not alter reward threshold and maximum rate of responding. Amphetamine produced a 25-30% decrease in reward threshold, an effect not altered by the highest dose of MPEP. At this dose, MPEP produced a weak inhibition of spontaneous locomotion and a significant attenuation of the enhanced locomotor activity induced by amphetamine. These findings show that mGLUR5 glutamate receptors are unlikely to constitute important elements of the reward-relevant pathway, and do not intervene in the enhancement effect of amphetamine. They also show, however, that these glutamate receptors play a key role in amphetamine-induced increased locomotor activity, providing additional evidence for a dissociation between the substrates that mediate these two behaviours.