Inhibitory actions of mGlu4 receptor ligands on cocaine-, but not nicotine-, induced sensitizing and conditioning locomotor responses in rats |
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| Affiliation: | 1. Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland;2. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland;3. Chemical and Pharmacokinetic Sciences, Lundbeck Research USA, Paramus, USA;1. Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovak Republic;2. Dept. of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA;3. Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville, Louisville, KY, USA;1. Karolinska Institutet, Department of Neurobiology, Care Science and Society, Center for Alzheimer Research, Novum level 5, 141 86 Stockholm, Sweden;2. European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany;3. Lund University, Department of Experimental Medical Science, Experimental Dementia Research Unit, Sölveg 19, BMC B12, 221 84 Lund, Sweden;1. Department of Mathematics, NCTS, National Cheng Kung University, Tainan 701, Taiwan;2. Institute of Applied Mathematics, NCTS (Taipei), National Taiwan University, Taipei 106, Taiwan |
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| Abstract: | BackgroundMale 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.MethodsThe 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.ResultsGiven 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.ConclusionsThe 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. |
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| Keywords: | Drugs of abuse Metabotropic glutamate 4 receptor ligands Sensitization Conditioned locomotor activity Rat |
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