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A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Cocaine self-administration markedly increases dopamine D2 receptor negative cooperativity for dopamine binding: A
Rafael Franco1, Philip Seeman, Carlos Barrera
1Department of Biochemistry and Molecular Biology, University of Barcelona, Diagonal 645, Barcelona, Spain. rfranco@unav.es
Synapse (New York, N.Y.)
|March 26, 2010
Summary
Cocaine use alters dopamine D(2) receptors, increasing the proportion of high-affinity receptors. This suggests cocaine impacts receptor function and cooperation, potentially contributing to dopamine supersensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Cocaine self-administration increases dopamine D(2)(High) receptors without altering total D(2) receptor numbers.
- Previous studies suggest a change in receptor availability or affinity.
Purpose of the Study:
- To re-analyze existing data on dopamine competition for [(3)H]domperidone binding in cocaine-addicted and naive animals.
- To investigate the impact of cocaine on dopamine D(2) receptor dimerization and function.
Main Methods:
- Analysis of competition binding data using dopamine competition assays.
- Modeling of dopamine D(2) receptors as constitutive dimers.
Main Results:
- Cocaine addiction alters dopamine D(2) receptor agonist affinity.
- Cocaine significantly affects receptor-receptor cooperation within D(2) receptor dimers.
- The proportion of D(2)(High) receptors increases post-cocaine self-administration.
Conclusions:
- Dopamine D(2) receptor dimerization is a key factor in understanding cocaine's effects.
- Altered receptor-receptor cooperation may underlie cocaine-induced dopamine supersensitivity.
- This dimer model provides a novel interpretation of cocaine's impact on D(2) receptor pharmacology.
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