Blockade of Adenosine A<sub>2A</sub>Receptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

Quiroz, César; Gomes, Catarina A.; Pak, Arlene C.; Ribeiro, Joaquim A.; Goldberg, Steven R.; Hope, Bruce T.; Ferré, Sergi

doi:10.1523/jneurosci.1661-06.2006

Cited by 26 publications

(27 citation statements)

References 30 publications

(40 reference statements)

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“…Because there is a likely coexpression of D1R and D2R in a significant percentage of MSNs (5-6% in the dorsal striatum and NAc core, 17% in the NAc shell), the apparently complete lack of ERK pathway activation in D2R neurons suggests that D2R may have an inhibitory effect on this pathway. Moreover, because the stimulation of corticostriatal projections activates ERK phosphorylation in D2R striatal neurons (Sgambato et al, 1998;Gerfen et al, 2002;Quiroz et al, 2006), results obtained in this study suggest that a basal DA tone could be repressing ERK activation in striatopallidal MSNs through D2R stimulation, which might act by opposing the action of glutamate and A 2a receptors. Additional studies are necessary to explore this possibility.…”

Section: Discussionmentioning

confidence: 67%

“…In DA-depleted striatum, stimulation of D1R activates ERK, which is linked to the development of dyskinesia (Gerfen et al, 2002;Pavon et al, 2006;Santini et al, 2007;Westin et al, 2007). Cortico-striatal stimulation also activates ERK in the dorsolateral striatum (Sgambato et al, 1998;Gerfen et al, 2002), partly by activating A 2a receptors (Quiroz et al, 2006). In contrast, antipsychotic drugs, which are antagonists at D 2 -like receptors, activate ERK in the striatum through an unknown mechanism (Pozzi et al, 2003;Hakansson et al, 2004;Valjent et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Bertran‐Gonzalez¹,

Bosch²,

Maroteaux³

et al. 2008

J. Neurosci.

536

501

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Psychostimulants and other drugs of abuse activate extracellular signal-regulated kinase (ERK) in the striatum, through combined stimulation of dopamine D 1 receptors (D1Rs) and glutamate NMDA receptors. Antipsychotic drugs activate similar signaling proteins in the striatum by blocking dopamine D 2 receptors (D2Rs). However, the neurons in which these pathways are activated by psychotropic drugs are not precisely identified. We used transgenic mice, in which enhanced green fluorescent protein (EGFP) expression was driven by D1R promoter (drd1a-EGFP) or D2R promoter (drd2-EGFP). We confirmed the expression of drd1a-EGFP in striatonigral and drd2-EGFP in striatopallidal neurons. Drd2-EGFP was also expressed in cholinergic interneurons, whereas no expression of either promoter was detected in GABAergic interneurons. Acute cocaine treatment increased phosphorylation of ERK and its direct or indirect nuclear targets, mitogen-and stress-activated kinase-1 (MSK1) and histone H3, exclusively in D1R-expressing output neurons in the dorsal striatum and nucleus accumbens. Cocaine-induced expression of c-Fos and Zif268 predominated in D1R-expressing neurons but was also observed in D2R-expressing neurons. One week after repeated cocaine administration, cocaine-induced signaling responses were decreased, with the exception of enhanced ERK phosphorylation in dorsal striatum. The responses remained confined to D1R neurons. In contrast, acute haloperidol injection activated phosphorylation of ERK, MSK1, and H3 only in D2R neurons and induced c-fos and zif268 predominantly in these neurons. Our results demonstrate that cocaine and haloperidol specifically activate signaling pathways in two completely segregated populations of striatal output neurons, providing direct evidence for the selective mechanisms by which these drugs exert their long-term effects.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Bertran‐Gonzalez¹,

Bosch²,

Maroteaux³

et al. 2008

J. Neurosci.

536

501

View full text Add to dashboard Cite

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“…Thus, in the context of reinstatement, ERK signalling within the basal ganglia has been defined as a molecular substrate for drug-paired contextual cue memories (Miller and Marshall, 2005). In rats, stimulation of corticostriatal afferents activate glutamatergic synapses within the basal ganglia resulting in phosphorylation of ERK and the Glu1 receptor subunit ; this can be prevented by pharmacological blockade of adenosine A 2A receptors (Quiroz et al, 2006). Whether heterodimeric A 2A -mGlu5 receptor complexes can synergize to regulate plasticity of the corticostriatal glutamate synapse awaits confirmation.…”

Section: Discussionmentioning

confidence: 99%

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Adams

Cowen

Short

et al. 2007

Int. J. Neuropsychopharm.

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Adenosine and glutamate have been implicated as mediators involved in the self-administration of alcohol. In the present study we sought to determine whether adenosine receptors could interact with metabotropic glutamate receptors to regulate operant responding for alcohol and also the integration of the salience of alcohol-paired cues. Alcohol-preferring (iP) rats were trained to self-administer alcohol under operant conditions. The availability of alcohol was paired with an olfactory cue plus a stimulus light. Rats were examined under fixed ratio responding and also following extinction under a cue-induced reinstatement paradigm. Administration of the selective adenosine A2A receptor antagonist, SCH 58261, reduced fixed ratio responding for alcohol in iP rats in a dose-related manner. Furthermore, the combination of a subthreshold dose of SCH 58261 with a subthreshold dose of the mGlu5 receptor antagonist MTEP also reduced alcohol self-administration and increased the latency to the first reinforced response, suggesting a pre-ingestive effect. Moreover, this combination of SCH 58261 and MTEP also prevented the conditioned reinstatement of alcohol-seeking elicited by the re-presentation of cues previously paired with alcohol availability. In contrast, combinations of the selective adenosine A1 receptor antagonist, DPCPX, with either SCH 58261 or MTEP had no effect on alcohol responding. Collectively, these data suggest a functional interaction between adenosine A2A and mGlu5 receptors in relation to alcohol-seeking and the integration of the drug-related cues.

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“…The parameters of cortical stimulation were the same as those shown previously to induce phosphorylation of ERK1/2 in cells of the projecting striatal area, the lateral caudate-putamen[28]. After 10 min of habituation, biphasic current pulse trains (pulse of 0.1 ms; 150–200 µA, 100 Hz, 160 ms trains repeating once per second) were delivered using two-coupled constant current units (Grass PSIU6; Grass Instruments).…”

Section: Methodsmentioning

confidence: 99%

Key Modulatory Role of Presynaptic Adenosine A_2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway

Quiroz

Luján

Uchigashima

et al. 2009

The Scientific World JOURNAL

123

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Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders.

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Blockade of Adenosine A_2AReceptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

Cited by 26 publications

References 30 publications

Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Key Modulatory Role of Presynaptic Adenosine A_2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway

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Blockade of Adenosine A2AReceptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

Cited by 26 publications

References 30 publications

Opposing Patterns of Signaling Activation in Dopamine D1and D2Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Opposing Patterns of Signaling Activation in Dopamine D1and D2Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Key Modulatory Role of Presynaptic Adenosine A2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway

Contact Info

Product

Resources

About

Blockade of Adenosine A_2AReceptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Key Modulatory Role of Presynaptic Adenosine A_2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway