Behavioral sensitization and cellular responses to psychostimulants are reduced in D2R knockout mice

Solís, Óscar; García‐Sanz, Patricia; Martín, Ana Belén Barragán; Granado, Noelia; Sanz-Magro, Adrián; Podlesniy, Petar; Trullàs, Ramón; Murer, Mario Gustavo; Maldonado, Rafaël; Moratalla, Rosario

doi:10.1111/adb.12840

Cited by 17 publications

(18 citation statements)

References 48 publications

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“…Both, D1R and D2R deletion and blockage differentially affected cocaine-induced behavioral sensitization. In line with previous studies, we found that D1 −/− mice had basal locomotor hyperactivity, while D2 −/− mice had basal locomotor hypoactivity (Karasinska et al, 2005;Karlsson et al, 2008;Miner, Drago, Chamberlain, Donovan, & Uhl, 1995;Solís et al, 2019). In agreement with these results, hypolocomotion and deficits in motor coordination and learning have been recently confirmed after inducible deletion of D2R in adult mice (Bello et al, 2017).…”

Section: Discussionsupporting

confidence: 93%

“…These alterations extend to either, the already described changes in cocaine-induced responses (Moratalla et al, 1996;Solís et al, 2019), and the plasma concentrations of BDNF, with a relevant influence of the sex steroids in rodents, as well as their variations along the estrous cycle. Both, D1R and D2R deletion and blockage differentially affected cocaine-induced behavioral sensitization.…”

Section: Discussionsupporting

confidence: 57%

“…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%

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…The classic model proposing the relative independence of the striatal pathways has recently been revised. Electrophysiology and calcium‐imaging data indicate functional interactions between d‐SPNs and i‐SPNs, which form neuronal clusters or ensembles during specific aspects of motor behavior, 58‐69 either by direct intrastriatal influence (SPN‐SPN) via interneurons, or multisynaptic connections with the motor cortex. Direct synaptic connections of d‐SPNs to i‐SPNs is supported by anatomical data revealing that collaterals synapses from d‐SPNs to i‐SPNs are weak 70,71 .…”

Section: Discussionmentioning

confidence: 99%

Dopamine D1 Receptors Regulate Spines in Striatal Direct‐Pathway and Indirect‐Pathway Neurons

et al. 2020

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Background Dopamine transmission is involved in the maintenance of the structural plasticity of direct‐pathway and indirect‐pathway striatal projection neurons (d‐SPNs and i‐SPNs, respectively). The lack of dopamine in Parkinson's disease produces synaptic remodeling in both types of SPNs, reducing the length of the dendritic arbor and spine density and increasing the intrinsic excitability. Meanwhile, the elevation of dopamine levels by levodopa recovers these alterations selectively in i‐SPNs. However, little is known about the specific role of the D1 receptor (D1R) in these alterations. Methods To explore the specific role of D1R in the synaptic remodeling of SPNs, we used knockout D1R mice (D1R−/−) and wild‐type mice crossed with drd2‐enhanced green fluorescent protein (eGFP) to identify d‐SPNs and i‐SPNs. Corticostriatal slices were used for reconstruction of the dendritic arbors after Lucifer yellow intracellular injection and for whole‐cell recordings in naïve and parkinsonian mice treated with saline or levodopa. Results The genetic inactivation of D1R reduces the length of the dendritic tree and the spine density in all SPNs, although more so in d‐SPNs, which also increases their spiking. In parkinsonian D1R−/− mice, the spine density decreases in i‐SPNs, and this spine loss recovers after chronic levodopa. Conclusions D1R is essential for the maintenance of spine plasticity in d‐SPNs but also affects i‐SPNs, indicating an important crosstalk between these 2 types of neurons. © 2020 International Parkinson and Movement Disorder Society

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“…For all of our studies, we used mice between 3- and 6-month-old (25–30 g). Genotype was determined by PCR analysis ( Solis et al. 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse

et al. 2020

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Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2−/−) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory.

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Behavioral sensitization and cellular responses to psychostimulants are reduced in D2R knockout mice

Cited by 17 publications

References 48 publications

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

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

Dopamine D1 Receptors Regulate Spines in Striatal Direct‐Pathway and Indirect‐Pathway Neurons

Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse

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