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.
Highlights
Metabotropic glutamate receptor 5 is a receptor that is thought to regulate anxiety and drug reward, though the mechanisms remain uncertain [1,2,3,4,5,6]
Analysis of FR-1 operant responding for food reinforcer revealed no significant effect of Metabotropic glutamate receptor 5 (mGluR5) genotype on either active (F(2,91) = 0.9, n.s.) or inactive lever pressing (F(2,91) = 1.1, n.s.), there was a significant effect of session number on active (F(7,91) = 12.4, p,0.0001), but not inactive (F(7,91) = 1.1, n.s.) lever pressing (Fig. 1B,D)
We have previously demonstrated that C57Bl/6J mice selfadminister varied visual and auditory cues in operant sessions without any prior training, a phenomenon we term ‘‘operant sensation seeking’’ (OSS) [18,19]
Summary
Metabotropic glutamate receptor 5 (mGluR5) is a receptor that is thought to regulate anxiety and drug reward, though the mechanisms remain uncertain [1,2,3,4,5,6]. We have recently described a method of assessing non-drug reinforcement by ‘‘self-administration’’ of varied sensory stimuli, a method we termed ‘‘operant sensation seeking’’ (OSS) [18,19] This procedure is based on a phenomenon whereby animals of several species will perform operant responses for visual and/or auditory stimuli [20,21,22,23,24]. We found that mGluR5 heterozygous did not show a phenotype in any other measures and that alterations in locomotor or anxietyrelated behavior do not appear to be responsible for the differences in OSS In total these data suggest a unique role for mGluR5 in reinforcement-based behavior
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