Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum

Ferré, Sergi; Sarasola, Laura I; Quiroz, César; Ciruela, Francisco

doi:10.1016/j.neuropharm.2022.109329

Cited by 28 publications

(6 citation statements)

References 125 publications

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“…A 2A R are also present at corticostriatal terminals ( Hettinger et al, 2001 ; Rebola et al, 2005 ), where they modulate glutamate release ( Ciruela et al, 2006 ; Rodrigues et al, 2005 ), controlling A 1 R ( Ciruela et al, 2006 ), CB 1 R ( Ferreira et al, 2015 ; Martire et al, 2011 ) and mGlu5R ( Rodrigues et al, 2005 ). Thus, A 2A R are uniquely positioned to integrate incoming information (glutamate signals) and neuronal sensitivity to this incoming information (dopamine signals) ( Ferré et al, 2023 ) to control striatal synaptic plasticity (long-term depression - LTD and long-term potentiation - LTP) and different striatum-dependent behaviors including goal-directed behavior. Accordingly, A 2A R modulate LTP at corticoaccumbal synapses ( d’Alcantara et al, 2001 ) and LTP, LTD ( Li et al, 2015a ; Maltese et al, 2017 ; Morató et al, 2019 ) and spike-timing-dependent LTP ( Flajolet et al, 2008 ; Shen et al, 2008a ) at glutamatergic synapses onto striatopallidal MSN.…”

Section: Striatopallidal a 2a R Exert Fine-tuning ...mentioning

confidence: 99%

Striatopallidal adenosine A2A receptor modulation of goal-directed behavior: Homeostatic control with cognitive flexibility

2023

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Section: Striatopallidal a 2a R Exert Fine-tuning ...mentioning

confidence: 99%

Striatopallidal adenosine A2A receptor modulation of goal-directed behavior: Homeostatic control with cognitive flexibility

2023

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“…Recent interesting findings on prefrontal cortex astrocytes indicated a significant functional interaction between α 1 -adrenergic and DA receptors, driving downstream Ca 2+ signaling [112]. Also, in light of the abovementioned data showing that DA receptors may form receptor complexes with adrenergic receptors [109,134], and of neuroanatomical data showing that D 1 and α 1 -adrenergic receptors colocalize on prefrontal cortex dendrites and may undergo co-trafficking [119], the hypothesis has been put forward that in cortical astrocytes as well, heterodimers involving DA receptors and adrenergic receptors could be present [112]. A direct experimental demonstration, however, is still lacking.…”

Section: Receptor Complexes Involving D 1 -Like Dopamine Receptorsmentioning

confidence: 94%

Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor–Receptor Interactions

Guidolin,

Tortorella,

Marcoli

et al. 2023

Pharmaceuticals

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Dopamine neurotransmission plays critical roles in regulating complex cognitive and behavioral processes including reward, motivation, reinforcement learning, and movement. Dopamine receptors are classified into five subtypes, widely distributed across the brain, including regions responsible for motor functions and specific areas related to cognitive and emotional functions. Dopamine also acts on astrocytes, which express dopamine receptors as well. The discovery of direct receptor–receptor interactions, leading to the formation of multimeric receptor complexes at the cell membrane and providing the cell decoding apparatus with flexible dynamics in terms of recognition and signal transduction, has expanded the knowledge of the G-protein-coupled receptor-mediated signaling processes. The purpose of this review article is to provide an overview of currently identified receptor complexes containing dopamine receptors and of their modulatory action on dopamine-mediated signaling between neurons and between neurons and astrocytes. Pharmacological possibilities offered by targeting receptor complexes in terms of addressing neuropsychiatric disorders associated with altered dopamine signaling will also be briefly discussed.

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“…As pre- and postsynaptic ADORA1s and ADORA2As play different roles in the regulation of neural signaling (Fredholm et al, 2005 ; Chen J.-F. et al, 2014 ; Ferré et al, 2023 ), the contradictory observations could be related to differences in the intrinsic preference for pre- or postsynaptic receptor populations among the tested compounds summarized in Table 1 . It has been shown that ADORA2A antagonists are distinguishable according to their preference for pre- vs. postsynaptic ADORA2As in the striatum (Orru et al, 2011 ).…”

Section: Adenosine Hypofunction In Schizophreniamentioning

confidence: 99%

The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks

Singer

Yee²

2023

Front. Cell. Neurosci.

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The adenosine hypothesis of schizophrenia was conceptualized about two decades ago in an attempt to integrate two prominent theories of neurochemical imbalance that attribute the pathogenesis of schizophrenia to hyperfunction of the mesocorticolimbic dopamine neurotransmission and hypofunction of cortical glutamate neurotransmission. Given its unique position as an endogenous modulator of both dopamine and glutamate signaling in the brain, adenosine was postulated as a potential new drug target to achieve multiple antipsychotic actions. This new strategy may offer hope for improving treatment, especially in alleviating negative symptoms and cognitive deficits of schizophrenia that do not respond to current medications. To date, however, the adenosine hypothesis has yet led to any significant therapeutic breakthroughs. Here, we address two possible reasons for the impasse. First, neither the presence of adenosine functional deficiency in people with schizophrenia nor its causal relationship to symptom production has been satisfactorily examined. Second, the lack of novel adenosine-based drugs also impedes progress. This review updates the latest preclinical and clinical data pertinent to the construct validity of the adenosine hypothesis and explores novel molecular processes whereby dysregulation of adenosine signaling could be linked to the etiology of schizophrenia. It is intended to stimulate and revitalize research into the adenosine hypothesis towards the development of a new and improved generation of antipsychotic drugs that has eluded us for decades.

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Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum

Cited by 28 publications

References 125 publications

Striatopallidal adenosine A2A receptor modulation of goal-directed behavior: Homeostatic control with cognitive flexibility

Striatopallidal adenosine A2A receptor modulation of goal-directed behavior: Homeostatic control with cognitive flexibility

Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor–Receptor Interactions

The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks

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