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

Chen, Jiang‐Fan; Moratalla, Rosario; Impagnatiello, Francesco; Grandy, David K.; Cuéllar, B.; Rubinstein, Marcelo; Beilstein, Mark A.; Hackett, Elizabeth; Fink, J. Stephen; Low, Malcolm J.; Ongini, Ennio; Schwarzschild, Michael A.

doi:10.1073/pnas.98.4.1970

Cited by 239 publications

(156 citation statements)

References 47 publications

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“…This has been shown in several experimental models including rodents pretreated with D 2 receptor antagonists, reserpine, 6-OH-dopamine or MPTP or after genetic inactivation of D 2 receptors (Kanda et al, 1994;Pollack and Fink, 1995;Shiozaki et al, 1999;Ward and Dorsa, 1999;Chen et al, 2001, Ferré et al, 2001Hauber et al, 2001;Wardas et al, 2001) or MPTP-treated monkeys (Kanda et al, 1998;Grondin et al, 1999). Reserpinized mice, rats with unilateral 6-OH-dopamine lesions and MPTP-treated monkeys are well-established validated models of Parkinson's disease.…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And The Acumentioning

confidence: 92%

“…The sleep-wake patterns of A 1 receptor knockout mice of the inbred C57BL/6 strain generated by Dr. Fredholm and collaborators (Johansson et al, 2001) and of A 2A receptor knockout mice generated by Dr. Chen and collaborators (Chen et al, 2001) were compared with those of wildtype mice. Both knockout mice showed clear circadian variations of sleep-stage distribution during basal conditions, similar to WT mice (Fig.…”

Section: Sleep-wake Regulation In Adenosine a 1 And A 2a Receptor Knomentioning

confidence: 99%

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Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

127

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Adenosine A 2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A 2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A 2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A 2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A 2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A 2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A 1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A 2A receptors. A 2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A 1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A 2A receptor knockout mice suggest that A 2A receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent.

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Section: Adenosine a 2a Receptors In The Ventral Striatum And The Acumentioning

confidence: 92%

Section: Sleep-wake Regulation In Adenosine a 1 And A 2a Receptor Knomentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

127

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“…Hence, when A2ARs are inactivated, it is not possible to activate adenylyl cyclase through the DRD2-blocker haloperidol, or to induce extended states of potentiation (Hakansson et al, 2006;Shen et al, 2008). Others have found that A2ARs are necessary for DRD2-induced changes in immediate-early gene expression (Chen et al, 2001). Thus, it is likely that genetic associations between inhibitory behavioral responses and genetic variants in the DRD2 gene would be dependent on genetic variability of these other members of the signaling cascade.…”

Section: Cellularmentioning

confidence: 99%

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Frank

Fossella

2010

Neuropsychopharmacol

171

167

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Many of the individual differences in cognition, motivation, and learningFand the disruption of these processes in neurological conditionsFare influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies. In this framework, genes modulate the efficacy of particular neural computations, and effects of genetic variation are revealed by assays designed to be maximally sensitive to these computations. We discuss the merits and caveats of this approach and outline a number of novel candidate genes of interest for future study.

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“…Although there are at least four types of adenosine receptors, adenosine A 2A receptors are primarily localized in striatal regions (DeMet and Chicz-DeMet, 2002;Jarvis and Williams, 1989), especially on the dendritic spines of GABAergic striatopallidal neurons (Ferré et al, 2004;Schiffmann et al, 1991). Considerable evidence indicates that there is a functional interaction between DA and adenosine A 2A receptors in both dorsal and ventral striatal areas (Chen et al, 2001;Hettinger et al, 2001;Svenningsson et al, 1999;Wang et al, 2000). This interaction often has been studied in the context of animal models related to parkinsonism, which typically focus on neostriatal motor functions (Ferré et al, , 2001Hauber et al, 2001;Ishiwari et al, 2007;Jenner, 2003Jenner, , 2005Morelli and Pinna, 2001;Pinna et al, 2005;Svenningsson et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Mingote

Pereira

Farrar

et al. 2008

Pharmacology Biochemistry and Behavior

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Adenosine A 2A receptors are involved in the regulation of several behavioral functions. Adenosine A 2A antagonists exert antiparkinsonian effects in animal models, and adenosine A 2A agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A 2A agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ratio 5 lever pressing were assessed. In the second experiment, rats were tested in 30 min feeding sessions, and also were observed for drug-induced sedation using a sedation rating scale. CGS 21680 (0.025, 0.05, 0.1 mg/kg IP) produced a dose related suppression of lever pressing, and also reduced the amount of food consumed. The feeding effect was largely dependent upon a slowing of the rate of feeding, and there was only a modest suppression of time spent feeding. Doses of CGS 21680 that suppressed lever pressing and feeding also were associated with sedation/drowsiness. In conjunction with other studies, the present results suggest that sedative effects may play an important role in some of the behavioral effects produced by systemic administration of adenosine A 2A agonists.

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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

Cited by 239 publications

References 47 publications

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

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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

Cited by 239 publications

References 47 publications

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Contact Info

Product

Resources

About

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