Modulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations

Andrianarivelo, Andry; Saint-Jour, Estefani; Walle, Roman; Trifilieff, Pierre; Vanhoutte, Peter

doi:10.1016/j.neuropharm.2018.12.003

Cited by 17 publications

(16 citation statements)

References 109 publications

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“…The focus on dopamine and NMDA receptor heteromers as potential integrators of dopamine and glutamate inputs that may control drug-mediated adaptations stems from in vitro and ex vivo studies showing that such a direct physical interaction allows a reciprocal fine-tuning of the component receptors' functions (23,27).…”

Section: Discussionmentioning

confidence: 99%

“…proposed as integrators of dopamine and glutamate signals in both MSN populations (23). Receptor heteromers are of particular interest, not only because of their ability to dynamically modulate the component receptor's functions in time and space, but also because they exhibit functional properties distinct from the component receptors, making them attractive targets for the development of more selective pharmacological strategies (24)(25)(26)(27).…”

Section: Heteromeric Complexes Formed Between Dopamine Receptors (Darmentioning

confidence: 99%

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Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

Andry

Estefani

Paula

et al. 2021

Preprint

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Addictive drugs increase dopamine in the nucleus accumbens (NAc), where it persistently shapes excitatory glutamate transmission and hijacks natural reward processing. Herein, we provide evidence, from mice to human, that an underlying mechanism relies on drug-evoked heteromerization of glutamate NMDA receptors (NMDAR) with dopamine receptor 1 (D1R) or 2 (D2R). Using temporally-controlled inhibition of D1R-NMDAR heteromerization, we unraveled their selective implication in early developmental phases of cocaine-mediated synaptic, morphological and behavioral responses. In contrast, preventing D2R-NMDAR heteromerization blocked the persistence of these adaptations. Importantly, interfering with these heteromers spared natural reward processing. Strikingly, we established that D2R-NMDAR complexes exist in human samples and showed that, despite a decreased D2R protein expression in the NAc, psychostimulant-addicts display a higher proportion of D2R forming heteromers with NMDAR. These findings contribute to a better understanding of molecular mechanisms underlying addiction and uncover D2R-NMDAR heteromers as targets with potential therapeutic value.

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Section: Discussionmentioning

confidence: 99%

Section: Heteromeric Complexes Formed Between Dopamine Receptors (Darmentioning

confidence: 99%

Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

Andry

Estefani

Paula

et al. 2021

Preprint

Self Cite

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“…The physical interaction of DA receptors with other receptors also appears as a powerful mechanism by which receptors can mutually modify their functions through allosteric interactions resulting in functional selectivity. Hence, receptor heteromers are emerging as promising targets for fine-tuning of specific signaling pathways (96)(97)(98). One of the bestcharacterized receptor complexes is D 2 R-A 2A R heteromers, which are detected in vivo in the striatum (99) and whose implication in reward and addiction is well reviewed (98,100).…”

Section: Cell-type-specific Striatal Signaling From the Membrane Towamentioning

confidence: 99%

“…Hence, receptor heteromers are emerging as promising targets for fine-tuning of specific signaling pathways (96)(97)(98). One of the bestcharacterized receptor complexes is D 2 R-A 2A R heteromers, which are detected in vivo in the striatum (99) and whose implication in reward and addiction is well reviewed (98,100). The key role of DA receptor-NMDAR interaction for their reciprocal modulation (101-104) makes these heteromers particularly relevant for addiction.…”

Section: Cell-type-specific Striatal Signaling From the Membrane Towamentioning

confidence: 99%

From Signaling Molecules to Circuits and Behaviors: Cell-Type–Specific Adaptations to Psychostimulant Exposure in the Striatum

Salery

Trifilieff

Caboche

et al. 2020

Biological Psychiatry

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Addiction is characterized by a compulsive pattern of drug seeking and consumption and a high risk of relapse after withdrawal that are thought to result from persistent adaptations within brain reward circuits. Drugs of abuse increase dopamine (DA) concentration in these brain areas, including the striatum, which shapes an abnormal memory trace of drug consumption that virtually highjacks reward processing. Long-term neuronal adaptations of gammaaminobutyric acidergic striatal projection neurons (SPNs) evoked by drugs of abuse are critical for the development of addiction. These neurons form two mostly segregated populations, depending on the DA receptor they express and their output projections, constituting the so-called direct (D 1 receptor) and indirect (D 2 receptor) SPN pathways. Both SPN subtypes receive converging glutamate inputs from limbic and cortical regions, encoding contextual and emotional information, together with DA, which mediates reward prediction and incentive values. DA differentially modulates the efficacy of glutamate synapses onto direct and indirect SPN pathways by recruiting distinct striatal signaling pathways, epigenetic and genetic responses likely involved in the transition from casual drug use to addiction. Herein we focus on recent studies that have assessed psychostimulant-induced alterations in a celltype-specific manner, from remodeling of input projections to the characterization of specific molecular events in each SPN subtype and their impact on long-lasting behavioral adaptations. We discuss recent evidence revealing the complex and concerted action of both SPN populations on drug-induced behavioral responses, as these studies can contribute to the design of future strategies to alleviate specific behavioral components of addiction.

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“…Dopaminergic receptors, which are classified as D1‐like receptors (D1, D5) and D2‐like receptors (D2, D3, D4), are primary expressed in segregated populations of MSN that constitute the so called direct and indirect pathways. These pathways act by exerting functional dichotomy in motor and reward‐dependent behavior integrating motivation, pleasure, attention, and cognitive functions (Andrianarivelo, Saint‐Jour, Walle, Trifilieff, & Vanhoutte, 2019; Gerfen & Surmeier, 2011; Karasinska, George, Cheng, & O'Dowd, 2005; Karlsson, Hefner, Sibley, & Holmes, 2008; Mishra, Singh, Tiwari, Parul, & Shukla, 2019; Solís et al, 2019; Thanos et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Sex‐specific behavioral and neurogenic responses to cocaine in mice lacking and blocking dopamine D1 or dopamine D2 receptors

Rivera

Aranda

Alén

et al. 2020

J of Comparative Neurology

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Adult neurogenesis in rodents is modulated by dopaminergic signaling and inhibited by cocaine. However, the sex-specific role of dopamine D1 and D2 receptors (D1R, D2R) in the deleterious effect of cocaine on adult neurogenesis has not been described yet. Here, we explored sex differences in (a) cell proliferation (5 0-bromo-2 0deoxyuridine [BrdU]), (b) neural precursor (nestin), (c) neuronal phenotype (BrdU/ β3-tubulin), and (d) neuronal maturity (NeuN) in the subventricular zone (SVZ) of the lateral ventricles and striatum of mice with genetic deletion (D1 −/− , D2 −/−) or pharmacological blockage (SCH23390: 0.1 mg/kg/day/5 days; Raclopride: 0.3 mg/kg/ day/5 days) of D1R and D2R, and treated (10 mg/kg/day/5 days) and then challenged (5 mg/kg, 48 hr later) with cocaine. Results indicated that hyperactivity responses to cocaine were absent in D1 −/− mice and reduced in SCH23390-treated mice. Activity responses to cocaine were reduced in D2 −/− males, but absent in D2 −/− females and increased in Raclopride-treated females. D1R deletion blocked the deleterious effect of cocaine on SVZ cell proliferation in males. Cocaine-exposed D1 −/− males also had reduced neuronal phenotype of SVZ newborn cells and increased striatal neuronal maturity. D2 −/− mice had lower proliferative and neural precursor responses. Cocaine in D2 −/− females or coadministered with Raclopride in wild-type females improved SVZ cell proliferation, an effect that positively correlated with plasma brain-derived neurotrophic factor (BDNF) concentrations. In conclusion, the sex-specific D1R and D2R signaling on SVZ cell proliferation, neural progenitor and neuronal maturity is differentially perturbed by cocaine, and BDNF may be required to link D2R to neuroplasticity in cocaine addiction in females.

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Modulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations

Cited by 17 publications

References 109 publications

Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

From Signaling Molecules to Circuits and Behaviors: Cell-Type–Specific Adaptations to Psychostimulant Exposure in the Striatum

Sex‐specific behavioral and neurogenic responses to cocaine in mice lacking and blocking dopamine D1 or dopamine D2 receptors

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