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- Title
Reduced Cocaine Self-Administration in Muscarinic M<sub>5</sub> Acetylcholine Receptor-Deficient Mice.
- Authors
Thomsen, Morgane; Woldbye, David P. D.; Wörtwein, Gitta; Fink-Jensen, Anders; Wess, Jürgen; Caine, S. Barak
- Abstract
The reinforcing effects of cocaine have been related to increased extracellular concentrations of dopamine in the ventral striatum. Several studies suggest that M5 muscarinic receptors facilitate striatal dopamine release. We tested the hypothesis that the reinforcing effects of cocaine are decreased in M5 receptor-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. M5 receptor 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 M5 receptor deletion diminished the reinforcing effects of low doses of cocaine and identified specific conditions under which this may be observed.
- Subjects
COCAINE; MUSCARINIC receptors; CHOLINERGIC receptors; REINFORCEMENT (Psychology); DOPAMINE receptors
- Publication
Journal of Neuroscience, 2005, Vol 25, Issue 36, p8141
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2077-05.2005