ライフサイエンスコーパス: D2R

1 D2R is a G protein-coupled receptor (GPCR) that activate

2 D2R stimulation by its agonist, dopamine, causes desensi

3 D2R-mediated signaling in dopamine neurons is involved i

4 D2R-OE(NAc) did not alter baseline body weight, but incr

5 D2R-OE(NAc) mice of both sexes also showed glucose intol

6 ed by DA D(2)-like receptors including D(2) (D2R) and D(3) (D3R) receptors.

7 We generated a D2R knockdown (KD) mouse line and assessed both energy e

8 on properties of T-type Ca(2+) channels in a D2R-protein kinase A-dependent manner without affecting

9 Here, we report on the development of a D2R mutant that recruits arrestin but is devoid of G pro

10 lices from wild-type mice with quinpirole, a D2R agonist, but those changes were lacking in D2LR knoc

11 We show that a D2R-driven behavior, nestlet shredding, is similarly dri

12 D) using positron emission tomography with a D2R-selective radioligand insensitive to endogenous dopa

13 AP threshold of stellate cells by activating D2Rs.

14 completed a PET scan with the high affinity D2R tracer [18 F]fallypride.

15 Surprisingly, although D2Rs are classically assumed to signal through Gi/o-coup

16 ne (DA) release, we retrospectively analyzed D2R availability measures of 8 current smokers, 10 ex-sm

17 ted extracellular striatal acetylcholine and D2R-induced paradoxical ChI excitation, which was revers

18 Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are requi

19 ions may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.

20 These findings indicate that D1R and D2R modulate different stages of reversal learning throu

21 These results suggest that D1R and D2R signaling are differentially involved in the acquisi

22 In conclusion, the sex-specific D1R and D2R signaling on SVZ cell proliferation, neural progenit

23 rols, and the effects on clusters of D1R and D2R were quantified.

24 block dopamine D1 and D2 receptors (D1R and D2R) when the PTL was conjugated to an engineered cystei

25 Raclopride: 0.3 mg/kg/day/5 days) of D1R and D2R, and treated (10 mg/kg/day/5 days) and then challeng

26 that distinct contributions of D1R-MSNs and D2R-MSNs towards reward and motor behaviors are delineat

27 hanistic details of biased D2R/G-protein and D2R/beta-arrestin signaling in vivo has been challenging

28 earing require coordinated D2R/G-protein and D2R/beta-arrestin signaling.

29 ly attenuated sucrose operant responding and D2R activation or blockade in the NAc bidirectionally mo

30 s the presence of T-type Ca(2+) channels and D2Rs in the axon initial segments (AISs).

31 D1Rs and D2Rs are also present at presynaptic cortical terminals

32 mediated by dopamine D1 receptors (D1Rs) and D2Rs, which are highly expressed in medium spiny neurons

33 ipitations show an association with Pcm1 and D2Rs.

34 y depend on both G-protein and beta-arrestin D2R signaling.

35 2b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increa

36 PDs can act as pharmacological chaperones at D2R.

37 ng as competitive antagonists of dopamine at D2R.

38 n guanine nucleotide exchange experiments at D2R and consequently represent biased agonists favoring

39 d with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship

40 Activation of axonal D2Rs, not dendritic or somatic D2Rs, elevated the action

41 All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis function

42 e was also capable of discriminating between D2R compounds.

43 Links between D2R levels, cognitive performance, and suppression of th

44 exercise, there was no relationship between D2R and working memory at baseline or following exercise

45 The BRET signal between D2R-Luc and GFP2-K-Ras was robustly diminished after rec

46 y developed beta-arrestin2 (betaarr2)-biased D2R partial agonists to simultaneously target hyper- and

47 Furthermore, betaarr2-biased D2R agonism enhances firing of cortical fast-spiking int

48 ipsychotic-like effects of a betaarr2-biased D2R ligand are driven through both striatal antagonism a

49 acquiring the mechanistic details of biased D2R/G-protein and D2R/beta-arrestin signaling in vivo ha

50 ase anaplastic lymphoma kinase (ALK) blocked D2R desensitization in neurons in the ventral tegmental

51 iffer significantly between groups, blocking D2Rs significantly changed the composition of the sixfol

52 standing the signaling pathways activated by D2R is crucial to finding new therapeutic targets for th

53 r, nestlet shredding, is similarly driven by D2R/G-protein signaling.

54 xplains some of the side effects elicited by D2R blockers when used in neurological and psychiatric c

55 contrast, reversal learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal st

56 a receptor tyrosine kinase transactivated by D2R that promotes its internalization, possibly through

57 Transgenic knockout mice in which beta-cell D2R or D3R expression is eliminated exhibit diminished D

58 In conclusion, D2R-OE(NAc) alters glucose metabolism in both sexes but

59 Consequently, conditional D2R knockout mice displayed a significant reduction in d

60 at a subset of neurons in the NAc containing D2Rs.

61 n locomotion and rearing require coordinated D2R/G-protein and D2R/beta-arrestin signaling.

62 verexpressed D2Rs on nucleus accumbens core (D2R-OE(NAc)) neurons that endogenously express D2Rs, and

63 ry impairment, and changes in levels of D1R, D2R, and NMDAR progressively improved several days after

64 c role of dopamine D1 and D2 receptors (D1R, D2R) in the deleterious effect of cocaine on adult neuro

65 press either the DA D1 or D2 receptors (D1R, D2R).

66 he density of cell-surface and synaptic D1R, D2R, and NMDAR clusters were examined at different time

67 king status affects baseline dopamine D2/D3 (D2R) receptor availability and methylphenidate-induced d

68 dly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates.

69 Extinction in DA D2R KO mice occurred less rapidly compared with WT mice

70 ys reported here could further help decipher D2R ligand-induced arrestin-3 recruitment and traffickin

71 atures accompanied by changes (D1R decrease, D2R increase) in cell-surface dopamine receptor clusters

72 ERK/MAPK-deficient D2R-MSNs exhibited a significant reduction in dendritic

73 unds of types 1-3 consist of three different D2R pharmacophores bound to an affinity-generating lipop

74 ion in the mechanisms that underlie distinct D2R-dependent behaviors, and opening the door to more ta

75 In this study, we found that downregulating D2R expression selectively in striatal indirect-pathway

76 l and genetic attempts to block or eliminate D2R have led to controversial results that questioned th

77 ALK inhibitors could be useful in enhancing D2R signaling.

78 D2 receptor (D2R) antagonist (eticlopride), D2R agonist (quinpirole), corticotropin-releasing factor

79 R-OE(NAc)) neurons that endogenously express D2Rs, and tested mice of both sexes in the open field te

80 tude), compared with cells that only express D2Rs.

81 vents synaptic stimulation from facilitating D2R-induced ADPs, suggesting that this phenomenon depend

82 od was available only 7 h a day, only female D2R-OE(NAc) mice rapidly lost 25% of their initial body

83 Surprisingly, female D2R-OE(NAc) mice also rapidly lost 25% of their initial

84 Furthermore, D2R and D3R act in combination to mediate dopaminergic i

85 On the other hand, D2R-driven locomotion and rearing require coordinated D2

86 These findings highlight how D2R mostly relies upon balanced G-protein and beta-arres

87 ins high levels of D2Rs, we investigated how D2R activation modulates the neuronal intrinsic excitabi

88 ceptor tyrosine kinases, we also examined if D2R stimulation activated ALK signaling.

89 allenge to test the hypothesis that impaired D2R internalization in SZ leads to blunted late-phase di

90 The iMSN-D2Rs modulate neuronal activity and synaptic transmissio

91 reveal that dopamine modulation through iMSN-D2Rs influences the ability to self-initiate actions, as

92 disruption in dopamine signaling to cAMP in D2R-MSN.

93 In conclusion, the age-related decline in D2R was not linked to the age-related decline in sweetne

94 e examined whether individual differences in D2R availability were related to neural subjective value

95 can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes

96 nal phosphoprotein (DARPP-32) exclusively in D2R-expressing cells exhibited preferential D2R changes

97 alyses reveal an unforeseen heterogeneity in D2R-expressing striatal neuronal populations, underlying

98 otor learning deficits seen upon NF1 loss in D2R-MSN.

99 ulates opioid reward, whereas loss of NF1 in D2R-MSNs delays motor learning by impeding the formation

100 proteins versus beta-arrestin recruitment in D2R-BRET functional assays.

101 In contrast, loss of ERK/MAPK signaling in D2R-MSNs (indirect pathway) resulted in a profound hyper

102 c receptors (mAChRs), leading to a switch in D2R coupling from canonical G(i/o) to noncanonical beta-

103 Variation in D2Rs has also been implicated in schizophrenia, Tourette

104 eclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission

105 ctinib completely inhibited dopamine-induced D2R internalization.

106 nhibitor completely blocked dopamine-induced D2R internalization.

107 eurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice.

108 azole, are less efficacious in internalizing D2R than most of the antiparkinsonian agents.

109 by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics.

110 somedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs

111 by cocaine, and BDNF may be required to link D2R to neuroplasticity in cocaine addiction in females.

112 naling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-reg

113 In HC individuals, lower D2R-related binding in the dorsal putamen was associated

114 In contrast, male D2R-OE(NAc) mice maintained body weight during scheduled

115 Although cNIC mitigates D2R-mediated aberrant motor learning, cNIC has no effect

116 Moreover, D2R signaling also modulates cell proliferation and modi

117 ial exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in V

118 Stimulating mPFC D2R+ neurons disrupts normal social interaction.

119 bolic impairments arising from disrupted NAc D2R signaling are involved in compulsive and perseverati

120 Collectively, these results implicate NAc D2R in regulating both peripheral glucose levels and glu

121 th precisely timed phasic stimulation of NAc D2R cells.

122 Postsynaptically, i.e., in striatal neurons, D2R signaling controls complex functions such as motor a

123 The loss of normal D2R roles may contribute to disorders in which impaired

124 idol and phencyclidine indicates that normal D2R signaling homeostasis can be dramatically altered, i

125 pecific Npas2 knockdown in D1R-MSNs, but not D2R-MSNs, in the NAc reduced cocaine conditioned place p

126 tment can drive locomotion in the absence of D2R-mediated G protein signaling.

127 tine, treatment mitigates the acquisition of D2R-antagonist-induced aberrant motor learning in mice.

128 ation requires the coordinated activation of D2R in the bed nucleus of the stria terminalis and the c

129 striatal antagonism and cortical agonism of D2R-betaarr2 signaling.

130 n vitro as high-affinity partial agonists of D2R, antagonists of 5-HT6R, and blockers of SERT.

131 Antagonism of D2R signaling in the striatum is thought to be the prima

132 While the blockade of D2R induces generalized threat responses, its stimulatio

133 nts is largely mediated by acute blockade of D2R/G-protein signaling.

134 aled the overall fundamental contribution of D2R in motor functions and explains some of the side eff

135 after its temporally-controlled deletion of D2R.

136 s research makes the pioneering discovery of D2R-induced AP threshold plasticity in AISs of stellate

137 ts nonredundant and reiterating functions of D2R in support of ARM.

138 ts completed [(11)C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task o

139 dendritic currents and blunted the impact of D2R activation on spontaneous activity and neuronal exci

140 al results that questioned the importance of D2R in motor function.

141 cell-surface D1R clusters and an increase of D2R clusters associated with a decrease of PPI.

142 rease of cell-surface D1R and an increase of D2R clusters.

143 resent study investigated the involvement of D2R and D1R during the early (perseverative) phase of re

144 ed in mice with the constitutive knockout of D2R (D2RKO).

145 Alterations in mRNA levels of D2R and CRF1 were also assessed.

146 We have found that loss of D2R during adulthood causes severe motor impairments, in

147 s but significantly reduced the magnitude of D2R-dependent inhibitory somatodendritic currents and bl

148 tages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core

149 us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning

150 intaining the excitability and plasticity of D2R-MSNs.SIGNIFICANCE STATEMENT Alterations in ERK/MAPK

151 ntly of dopamine at an intracellular pool of D2R to enhance transport of D2R to the cell surface and

152 y neurons (iMSNs) in the ventral striatum of D2R knockout mice, this mutant restored basal locomotor

153 cellular pool of D2R to enhance transport of D2R to the cell surface and suggest that APDs can act as

154 Activation of D2Rs shifts the activation curve of T-type Ca(2+) channe

155 uorescence assays revealed colocalization of D2Rs and Ca(v) 3.2 calcium channels within the axon init

156 suggesting a possible switch in coupling of D2Rs to beta-arrestin, as seen previously in a DYT1 mode

157 Selective deletion of D2Rs from indirect pathway-projecting medium spiny neuro

158 Selective deletion of D2Rs on iMSNs resulted in slower action initiation and r

159 ying a novel signaling pathway downstream of D2Rs that may contribute to prefrontal function under no

160 s beta-arrestin, we find that the effects of D2Rs on prefrontal pyramidal neurons are actually mediat

161 Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other n

162 al cognition and MEC contains high levels of D2Rs, we investigated how D2R activation modulates the n

163 nistic bases for this dual signaling mode of D2Rs and how these new concepts might be leveraged for t

164 However, the role of D2Rs in the initiation of motor actions in reward seekin

165 that the effect of haloperidol antagonism on D2R metabolic signaling events is largely mediated by ac

166 DA neuron-specific loss of GIRK channels on D2R-dependent regulation of VTA DA neuron excitability a

167 Effects of ethnicity on D2R were not driven by variation in dopaminergic candida

168 fashion, confirming that this ADP depends on D2Rs.

169 Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spati

170 asured glutamatergic transmission at D1R- or D2R-expressing afferents to DMS MSNs.

171 We find that knocking out D2Rs eliminates the ADP in a cell-autonomous fashion, co

172 We virally overexpressed D2Rs on nucleus accumbens core (D2R-OE(NAc)) neurons tha

173 female Gnal (+/-) mice, but the paradoxical D2R-mediated ChI excitation was retained and only revers

174 In particular, D2R blockade shifted the balance of OFC connectivity fro

175 These results reveal that peripheral D2R and D3R receptors play important roles in metabolism

176 tensity, and striatal D2R binding potential (D2R BPND) using positron emission tomography with a D2R-

177 D2R-expressing cells exhibited preferential D2R changes in the nucleus accumbens (NAc), a striatal r

178 The G(i/o)-preferring D2R agonist failed to increase ChI excitability, suggest

179 , a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and

180 vation of postsynaptic, but not presynaptic, D2Rs inhibited corticostriatal transmission in an endoca

181 ne 1 receptor (D1R) and dopamine 2 receptor (D2R) and cause psychotic-like features in mice.

182 oss-talk between the dopamine D(2) receptor (D2R) and Wnt/beta-catenin signaling pathways.

183 d a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in s

184 Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disord

185 opiperazines with high dopamine D2 receptor (D2R) affinity.

186 interneurons (ChIs) by dopamine D2 receptor (D2R) agonism using ex vivo slice electrophysiology in Dy

187 (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase

188 ceived injections of a dopamine D2 receptor (D2R) antagonist (eticlopride), D2R agonist (quinpirole),

189 lacebo-controlled pharmacology [D2 receptor (D2R) antagonist amisulpride] in humans with resting-stat

190 is associated with low dopamine D2 receptor (D2R) availability in the striatum.

191 Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with ab

192 ecific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D

193 The dopamine D2 receptor (D2R) is a G protein-coupled receptor (GPCR) expressed in

194 The dopamine D2 receptor (D2R) is a G protein-coupled receptor that is a common ta

195 The dopamine D2 receptor (D2R) is a major component of the dopamine system.

196 The dopamine (DA) D2 receptor (D2R) is an important target for the treatment of neurops

197 by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to re

198 The dopamine D2 receptor (D2R) mediates ligand-biased signaling with potential the

199 eport that the modulation of DA D2 receptor (D2R) signaling bidirectionally regulates the consolidati

200 function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversia

201 s target primarily the dopamine D2 receptor (D2R) to inhibit G(i/o)-mediated adenylyl cyclase, a rece

202 suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ).

203 The dopamine D2 receptor (D2R), like many G-protein-coupled receptors, signals thr

204 y comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2L

205 d that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested th

206 GABAB receptor (GABABR) and D2 DA receptor (D2R) activation in VTA DA neurons.

207 iased agonist of the D(2) dopamine receptor (D2R) that results in impaired beta-arrestin recruitment.

208 ne receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs).

209 al differences in dopamine D2-type receptor (D2R) levels in the caudate nucleus and performance in a

210 r availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R).

211 tic drugs (APDs) bind dopamine D2 receptors (D2R) at therapeutic concentrations, and it is thought th

212 s, neurons expressing dopamine D2 receptors (D2R) in the dorsal striatum (DS) and the nucleus accumbe

213 sing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related

214 Blocking dopamine D2-receptors (D2R) altered generalization behavior as revealed by an i

215 mpletely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) litte

216 ual differences in human dopamine receptors (D2R) were related to cognitive performance before and af

217 striatal D(2)-like and D(1)-like receptors (D2R; D1R) in this form of flexibility, less is known abo

218 Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are impli

219 Striatal dopamine D2 receptors (D2Rs) are important for motor output.

220 Because dopamine D2 receptors (D2Rs) are involved in spatial cognition and MEC contains

221 p layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cr

222 that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs)

223 IGNIFICANCE STATEMENT Dopamine D2 receptors (D2Rs) in the prefrontal cortex (PFC) are thought to play

224 Activation of axonal dopamine D2 receptors (D2Rs) increases action potential (AP) threshold, and thu

225 ed by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum.

226 similar to most G protein-coupled receptors, D2Rs signal not only through canonical G protein pathway

227 cotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning.

228 It is often suggested that reduced D2R generates a reward deficiency and altered appetitive

229 leaving open the question of whether reduced D2R contributes to obesity through alterations in energy

230 thways downstream of ALK that might regulate D2R internalization, we used pharmacological inhibitors

231 ystem, we investigated whether ALK regulates D2R internalization.

232 lly, dopaminergic neurons themselves require D2R, suggesting a critical role in dopamine release via

233 pecific viral expression approach to restore D2R variants that preferentially engage either G-protein

234 As a result, D2R is involved in the pathophysiology of disorders such

235 c drug, phencyclidine, displayed a selective D2R/beta-arrestin potentiation of locomotion.

236 Lastly, beta-cell-selective D2R knockout mice exhibit marked postprandial hyperinsul

237 l BRET signals were blocked by the selective D2R antagonist haloperidol and were decreased by low tem

238 ion of axonal D2Rs, not dendritic or somatic D2Rs, elevated the action potential (AP) threshold and d

239 ltered, indicating that targeting a specific D2R signal transduction pathway could allow for more pre

240 t alone or in concert to facilitate specific D2R-dependent behaviors is unclear.

241 al neuronal populations, underlying specific D2R's functional features in the control of specific mot

242 omic sequences, we developed a new statistic D2R that can efficiently discriminate sequences with or

243 ception of sweetness intensity, and striatal D2R binding potential (D2R BPND) using positron emission

244 onship between genetic ancestry and striatal D2R.

245 ffect of smoking status on baseline striatal D2R availability; with current smokers showing lower str

246 Baseline striatal D2R did not differ between nonsmokers and ex-smokers.

247 Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously desc

248 However, both striatal D2R BPND and age correlated with sucrose preferences in

249 arkers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the N

250 s at the synapses between the extra-striatal D2R-expressing afferents and D1R-expressing MSNs (D2->D1

251 e show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-

252 nce ex-smokers may recover from low striatal D2R availability and from increased behavioral aggressio

253 with current smokers showing lower striatal D2R availability compared with nonsmokers (caudate, puta

254 By combining RNAseq of striatal D2R neurons and histological analyses, we identified hun

255 nts with SZ and HC, suggesting that striatal D2R internalization as measured by our imaging paradigm

256 d, candidate gene associations with striatal D2R were diminished when correcting for ancestry.

257 ect was potentiated in mice lacking striatal D2Rs from indirect-pathway neurons.

258 To our surprise, mice with low striatal D2Rs acquired cocaine self-administration similarly to l

259 ngs indicate that downregulation of striatal D2Rs triggers D1R hypersensitivity to facilitate cocaine

260 ositive correlation between ventral striatum D2R availability and subjective value-related activity i

261 Surprisingly, D2R inhibition of synaptic transmission was larger at ax

262 rane marker), and between luciferase8-tagged D2R and GFP2-Rab5 (early), GFP2-Rab4 (recycling), or GFP

263 distances between Renilla luciferase8-tagged D2R and green fluorescent protein 2 (GFP2)-tagged K-Ras

264 T signals increasing when luciferase8-tagged D2R approached GFP2-Rab proteins in endosomal compartmen

265 on G protein-coupled receptor (GPCR) target, D2R, could contribute to differences in their clinical p

266 These data reveal that D2R signaling in the extended amygdala constitutes an im

267 Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively

268 Our study revealed that D2R trafficking in cells was differentially regulated by

269 Together, our results suggest that D2R is a transcriptional modulator of Wnt/beta-catenin s

270 Our data suggest that D2R-dependent cross-talk modulates Wnt3a expression via

271 ed by Gs-DREADD stimulation, suggesting that D2R activation elicits the ADP by stimulating cAMP/PKA s

272 type Ca(2+) channels in MEC, indicating that D2Rs of MEC play a vital role in modulating the informat

273 1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively redu

274 cking those interactions of dopamine and the D2R that are crucial for an active state, leading to the

275 acious as antiparkinsonians in directing the D2R toward early and recycling endosomes.

276 these genetic models of human dystonia, the D2R-mediated paradoxical excitation of ChIs is shared an

277 We could show that some drugs engaged the D2R either to interact preferentially with arrestin-3 or

278 Finally, the D2R-induced ADP is blocked by inhibitors of cAMP/PKA sig

279 of endocytic routes, and degradation of the D2R in lysosomes may also participate in agonist-directe

280 Global genetic deletion of the D2R in mice disrupts reversal performance, indicating a

281 loop and fifth transmembrane segment of the D2R.

282 ne-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the

283 These D2R-induced ADPs only occur following synaptic input, wh

284 Furthermore, we show how, via this D2R-dependent phenomenon, synaptic input can enhance the

285 d with Stroop performance indirectly through D2R in HC and D3R in CUD participants, and these indirec

286 Though biased signaling through D2Rs has been demonstrated, acquiring the mechanistic de

287 se between DA and radiotracer for binding to D2R.

288 release and blunt postsynaptic responses to D2R antagonists.

289 nisms that have classically been ascribed to D2Rs.SIGNIFICANCE STATEMENT Dopamine D2 receptors (D2Rs)

290 ibited the lowest efficacy for translocating D2R to the cell surface.

291 in a manner indistinguishable from wild-type D2R, indicating that arrestin recruitment can drive loco

292 ve motivation was enhanced only by wild-type D2R, signifying a dissociation in the mechanisms that un

293 ith positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge

294 constant access to food and running wheels, D2R-OE(NAc) mice of both sexes increased food intake and

295 ion as an important molecular event by which D2R mediates its effects.

296 , we described a new mechanism through which D2R activation can enhance the excitability of pyramidal

297 provide a novel cellular mechanism by which D2Rs modulate AP threshold of stellate cells through T-t

298 s unusual physiological phenomenon, in which D2Rs enhance cellular excitability in a manner that depe

299 While D2R decreased (perhaps counterintuitively) with exercise

300 treatment and ALK coimmunoprecipitated with D2R.