title: Inhibitory actions of mGlu4 receptor ligands on cocaine-, but not nicotine-, induced sensitizing and conditioning locomotor responses in rats.
abstract: 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-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.
  
  
  RESULTS
  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.
  
  
  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, mGlu4 receptor activation seems to be devoid of any effect on the locomotor effects of nicotine.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: zaniew@if-pan.krakow.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zaniewska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Przegaliński
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
authors.affiliation: Chemical and Pharmacokinetic Sciences, Lundbeck Research USA, Paramus, USA.
authors.forename: Darío
authors.initials: D
authors.lastname: Doller
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D010721:Phosphinic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
chemical_list: D000613:Aminobutyrates; C555637:LSP1 2111; D008024:Ligands; D010721:Phosphinic Acids; D018094:Receptors, Metabotropic Glutamate; D009538:Nicotine; D003042:Cocaine; C108823:metabotropic glutamate receptor 4
keywords: Conditioned locomotor activity; Drugs of abuse; Metabotropic glutamate 4 receptor ligands; Rat; Sensitization