The mGlu5 receptor regulates extinction of cocaine-driven behaviours
| Autor: | Jeppe Kirchhoff, Clarke R. Raymond, Peter Lohmann, Billy West, Michael K. Bird, Andrew J Lawrence, Robyn M Brown |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Receptor Metabotropic Glutamate 5 Long-Term Potentiation Self Administration Water maze Toxicology Hippocampus Extinction Psychological Mice Organ Culture Techniques Cocaine Animals Pharmacology (medical) Mice Knockout Pharmacology Classical conditioning Long-term potentiation Extinction (psychology) Conditioned place preference Behavior Addictive Mice Inbred C57BL Psychiatry and Mental health Metabotropic receptor Metabotropic glutamate receptor Self-administration Psychology Neuroscience |
| Zdroj: | Drug and Alcohol Dependence. 137:83-89 |
| ISSN: | 0376-8716 |
| Popis: | Background There is extensive evidence implicating the metabotropic glutamate 5 (mGlu5) receptor in aspects of addiction-related behaviours. Methods Here, we used a well-characterized line of mGlu5-deficient mice to further examine the role of this receptor in cocaine-driven behaviours. We confirmed the previously reported deficit in hippocampal long-term potentiation and associated spatial learning impairment. Results Despite a spatial learning deficit, mGlu5-deficient mice developed and maintained a conditioned place preference to cocaine, suggesting cocaine reward and Pavlovian conditioning are intact in these animals. Notably, however, mGlu5-deficient mice exhibited a marked deficit in the extinction of a cocaine-conditioned place preference compared to wild type littermates. Moreover, in a fixed ratio operant intravenous self-administration paradigm, both genotypes showed similar responding for cocaine over two different doses, while mGlu5-deficient mice displayed enhanced responding on a progressive ratio schedule. In addition, cue-induced drug-seeking after abstinence was exaggerated in mGlu5-deficient mice. Conclusion Collectively, these findings suggest that while the mGlu5 receptor may be involved in mediating the rewarding effects of cocaine, it appears necessary for the extinction of cocaine-driven behaviours. |
| Databáze: | OpenAIRE |
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