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Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine, and Methamphetamine
Open accessAbstract
The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.
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Cites
The neural basis of drug craving: An incentive-sensitization theory of addiction
Robinson, T. (1993) · Brain Research Reviews · doi:10.1016/0165-0173(93)90013-p · Cited by 7,346
Neurotransmitters and neuromodulators in the basal ganglia
Graybiel, A. M. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90104-i · Cited by 1,576
Multiple dopamine D4 receptor variants in the human population
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Self-citationLocalization of dopamine D4 receptors in GABAergic neurons of the primate brain
Mrzljak, L., Bergson, C., Pappy, M., Huff, R., Levenson, R., & Goldman-Rakic, P. S. (1996) · Nature · doi:10.1038/381245a0 · Cited by 494
Synaptic regulation of mesocorticolimbic dopamine neurons
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Cited by
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624
Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020
The neurobiology and control of anxious states
Millan, M. J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00087-x · Cited by 965
Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli
Dulawa, S. C., Grandy, D. K., Low, M. J., Paulus, M. P., & Geyer, M. A. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09550.1999 · Cited by 431
Self-citationThe Genetic Architecture of Selection at the Human Dopamine Receptor D4 (DRD4) Gene Locus
Wang, E., Ding, Y.-C., Flodman, P., Kidd, J. R., Kidd, K. K., Grady, D. L., Ryder, O. A., Spence, M. A., Swanson, J. M., & Moyzis, R. K. (2004) · The American Journal of Human Genetics · doi:10.1086/420854 · Cited by 401
Metadata
- Authors
- Rubinstein, M., Phillips, T. J., Bunzow, J. R., Falzone, T. L., Dziewczapolski, G., Zhang, G., Fang, Y., Larson, J. L., McDougall, J. A., Chester, J. A., Saez, C., Pugsley, T. A., Gershanik, O., Low, M. J., & Grandy, D. K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-09
- Volume
- 90
- Issue
- 6
- Pages
- 991-1001
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1975977959
- Cited by
- 471
- References
- 5
- FWCI
- 9.88
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rubinstein, M., Phillips, T. J., Bunzow, J. R., Falzone, T. L., Dziewczapolski, G., Zhang, G., Fang, Y., Larson, J. L., McDougall, J. A., Chester, J. A., Saez, C., Pugsley, T. A., Gershanik, O., Low, M. J., & Grandy, D. K. (1997). Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine, and Methamphetamine. Cell. https://doi.org/10.1016/s0092-8674(00)80365-7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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