Zaniewska Magdalena, Przegaliński Edmund, Filip Małgorzata, Pilc Andrzej, Doller Darío
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Pharmacol Rep. 2014 Apr;66(2):205-11. doi: 10.1016/j.pharep.2013.12.001. Epub 2014 Mar 2.
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.
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-N(1)-(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 (10mg/kg), nicotine (0.4 mg/kg) or the respective vehicles for 5 days. On day 10, animals were challenged with cocaine (10mg/kg, cocaine sensitization), nicotine (0.4 mg/kg, nicotine sensitization) or vehicle (conditioned hyperlocomotion) in experimental cages.
Given on day 10, LSP1-2111 (3mg/kg) as well as Lu AF21934 (2.5-5mg/kg) decreased the expression of cocaine sensitization. In another set of experiments, LSP1-2111 (3mg/kg) and Lu AF21934 (5mg/kg) administered on day 10 attenuated the conditioned hyperlocomotion in rats treated repeatedly with cocaine. Neither LSP1-2111 (1-3mg/kg) nor Lu AF21934 (2.5-5mg/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.
The present data indicate that pharmacological stimulation of mGlu4 receptors reduces the cocaine-induced expression of sensitization as well as conditioned hyperactivity. In contrast, mGlu4 receptor activation seems to be devoid of any effect on the locomotor effects of nicotine.
