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-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.
['Zaniewska|Magdalena|M|', 'Przegaliński|Edmund|E|', 'Filip|Małgorzata|M|', 'Pilc|Andrzej|A|', 'Doller|Darío|D|']
D000613:Aminobutyrates D000818:Animals D003042:Cocaine D003213:Conditioning, Psychological D008024:Ligands D008297:Male D009043:Motor Activity D009538:Nicotine D010721:Phosphinic Acids D051381:Rats D017208:Rats, Wistar D018094:Receptors, Metabotropic Glutamate
Sensitization Rat Conditioned locomotor activity Drugs of abuse Metabotropic glutamate 4 receptor ligands