title: Operant sensation seeking requires metabotropic glutamate receptor 5 (mGluR5).
abstract: Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. chris.olsen@vanderbilt.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Olsen
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Childs
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Stanwood
authors.forename: Danny G
authors.initials: DG
authors.lastname: Winder
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000502:physiology*; D005260:Female; D005838:Genotype; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration; D012677:Sensation / Q000235:genetics / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014662:Vasoconstrictor Agents; D003042:Cocaine