Inhibitory actions of mGlu4 receptor ligands on cocaine-,but not nicotine-,induced sensitizing and conditioning locomotor responses in rats

Background: male wistar rats were used to verify the hypothesis that metabotropic glutamate 4 (mglu4) receptor ligands may modulate the locomotor effects evoked by cocaine or nicotine. methods: the preferential mglu4 receptor orthosteric agonist (2s)-2-amino-4-[hydroxy[hydroxy(4- hydroxy-3-methoxy-5-nitrophenyl)methyl]phosphoryl]butanoic acid (lsp1-2111) and the mglu4 receptor positive allosteric modulator (+)-cis-n1-(3,4-dichlorophenyl)cyclohexane-1,2-dicarboxamide (lu af21934) were used in the study. rats were given repeated pairings of a test environment with cocaine (10 mg/kg),nicotine (0.4 mg/kg) or the respective vehicles for 5 days. on day 10,animals were challenged with cocaine (10 mg/kg,cocaine sensitization),nicotine (0.4 mg/kg,nicotine sensitization) or vehicle (conditioned hyperlocomotion) in experimental cages. results: given on day 10,lsp1-2111 (3 mg/kg) as well as lu af21934 (2.5-5 mg/kg) decreased the expression of cocaine sensitization. in another set of experiments,lsp1-2111 (3 mg/kg) and lu af21934 (5 mg/kg) administered on day 10 attenuated the conditioned hyperlocomotion in rats treated repeatedly with cocaine. neither lsp1-2111 (1-3 mg/kg) nor lu af21934 (2.5-5 mg/kg) changed the expression of nicotine sensitization and conditioned hyperlocomotion in rats treated repeatedly with nicotine. none of the mglu4 receptor agonist/modulator altered the basal locomotor activity or acute hyperactivity to cocaine or nicotine. conclusions: the present data indicate that pharmacological stimulation of mglu4 receptors reduces the cocaine-induced expression of sensitization as well as conditioned hyperactivity. in contrast,mglu 4 receptor activation seems to be devoid of any effect on the locomotor effects of nicotine. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban & partner sp. z o.o. all rights reserved.