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.
Gormley
Stéphanie
S
Hôpital Louis-H. Lafontaine, Montréal, Québec, Canada. pierre-paul.rompre@umontreal.ca
Rompré
Pierre-Paul
PP
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D012201:Reward
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D000661:Amphetamine