The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
The role of the D 2 dopamine receptor (D 2 R) in A 2A adenosine receptor (A 2A R)-mediated behavioral and cellular responses as revealed by A 2A and D 2 receptor knockout mice
Open accessAbstract
The A 2A R is largely coexpressed with D 2 Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A 2A R antagonizes D 2 R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A 2A R–D 2 R interaction. However, whether the D 2 R is required for the A 2A R to exert its neural function is an open question. In this study, we examined the role of D 2 Rs in A 2A R-induced behavioral and cellular responses, by using genetic knockout (KO) models (mice deficient in A 2A Rs or D 2 Rs or both). Behavioral analysis shows that the A 2A R agonist 2–4-(2-carboxyethyl)phenethylamino-5′- N -ethylcarboxamidoadenosine reduced spontaneous as well as amphetamine-induced locomotion in both D 2 KO and wild-type mice. Conversely, the nonselective adenosine antagonist caffeine and the A 2A R antagonist 8-(3-chlorostyryl)caffeine produced motor stimulation in mice lacking the D 2 R, although the stimulation was significantly attentuated. At the cellular level, A 2A R inactivation counteracted the increase in enkephalin expression in striatopallidal neurons caused by D 2 R deficiency. Consistent with the D 2 KO phenotype, A 2A R inactivation partially reversed both acute D 2 R antagonist (haloperidol)-induced catalepsy and chronic haloperidol-induced enkephalin mRNA expression. Together, these results demonstrate that A 2A Rs elicit behavioral and cellular responses despite either the genetic deficiency or pharmacological blockade of D 2 Rs. Thus, A 2A R-mediated neural functions are partially independent of D 2 Rs. Moreover, endogenous adenosine acting at striatal A 2A Rs may be most accurately viewed as a facilitative modulator of striatal neuronal activity rather than simply as an inhibitory modulator of D 2 R neurotransmission.
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Self-citationA2AAdenosine Receptor Deficiency Attenuates Brain Injury Induced by Transient Focal Ischemia in Mice
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International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors
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Caffeine as a psychomotor stimulant: mechanism of action
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Dopamine Dysregulation Syndrome: An Overview of its Epidemiology, Mechanisms and Management
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Metadata
- Authors
- Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D. K., Cuellar, B., Rubinstein, M., Beilstein, M. A., Hackett, E., Fink, J. S., Low, M. J., Ongini, E., & Schwarzschild, M. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-02-13
- Volume
- 98
- Issue
- 4
- Pages
- 1970-1975
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2092666379
- Cited by
- 256
- References
- 41
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, J.-F., Moratalla, R., Impagnatiello, F., Grandy, D. K., Cuellar, B., Rubinstein, M., Beilstein, M. A., Hackett, E., Fink, J. S., Low, M. J., Ongini, E., & Schwarzschild, M. A. (2001). The role of the D 2 dopamine receptor (D 2 R) in A 2A adenosine receptor (A 2A R)-mediated behavioral and cellular responses as revealed by A 2A and D 2 receptor knockout mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.98.4.1970
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