Reduced Cocaine Self-Administration in Muscarinic M5Acetylcholine Receptor-Deficient Mice
Open Access
- 7 September 2005
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 25 (36) , 8141-8149
- https://doi.org/10.1523/jneurosci.2077-05.2005
Abstract
The reinforcing effects of cocaine have been related to increased extracellular concentrations of dopamine in the ventral striatum. Several studies suggest that M5muscarinic receptors facilitate striatal dopamine release. We tested the hypothesis that the reinforcing effects of cocaine are decreased in M5receptor-deficient mice using chronic intravenous cocaine self-administration in extensively backcrossed mice. We also assessed whether operant performance generally, rather than cocaine self-administration specifically, was altered in the mutant mice. To this end, we evaluated both food-maintained operant behavior and cocaine self-administration under a fixed ratio 1 and a progressive ratio (PR) schedule of reinforcement. We also evaluated acquisition of self-administration in experimentally naive mice using several doses of cocaine. M5receptor deletion decreased self-administration of low to moderate doses of cocaine under a PR schedule of reinforcement and diminished acquisition of self-administration of a low dose in experimentally naive mice. We found no differences between genotypes in food-maintained behavior. The present study extends our previous findings using backcrossed mice and covering various experimental conditions. Our results indicate that M5receptor deletion diminished the reinforcing effects of low doses of cocaine and identified specific conditions under which this may be observed.Keywords
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