ライフサイエンスコーパス: D2R

1 D2R is a prominent target for drug treatments in disorde

2 D2R signals through distinct G-protein and beta-arrestin

3 D2R slowed the endocytosis of Ca(V)2.2 containing exon 3

4 D2R-mediated signaling in dopamine neurons is involved i

5 D2R-OE mice display deficits in cognition and motivation

6 D2Rs expressed by midbrain DA neurons function as autore

7 In the Ca(2+)/NCS-1.D2R peptide complex, the C-terminal region adopts a 310

8 ty occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), si

9 Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and

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

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

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

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

14 be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR a

15 ock an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity

16 ric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy.

17 confirmed that current evidence for altered D2R availability in obesity is only modest.

18 suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expendit

19 vidence on the effects of obesity on altered D2R availability.

20 th a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity.

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

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

23 as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with biol

24 Haloperidol, a typical antipsychotic and D2R blocker, reduced AMPH hypersensitivity and elevated

25 istochemistry to map dorsal-striatal D1R and D2R expression at the promoter level in postnatal day 0

26 eptor level by costaining for native D1R and D2R in wildtype (WT) PD0 animals.

27 expression and colocalization of the D1R and D2R proteins was found in clusters of neurons endemic to

28 ntial molecular interactions between D1R and D2R we also employed a recently developed proximity-liga

29 G protein signaling at DA receptors (D1R and D2R) in addition to activating their own G protein-indep

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

31 antiviral effect against DENV infection, and D2R may play a role in the DENV life cycle.

32 ons required activation of both D1R-like and D2R-like receptors.

33 nctional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.

34 ge-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [

35 cant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated.

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

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

38 oved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functio

39 associated low striatal dopamine release and D2R binding with alcohol dependence.

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

41 cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellula

42 ovel pathway regulating striatal DA tone and D2R signaling.

43 mediated by both D1-like receptors (D1R) and D2Rs.

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

45 2b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increa

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

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

48 multiple regions of aripiprazole, a balanced D2R agonist.

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

50 ether there is a causal relationship between D2R levels and alcohol intake.

51 ns of the striatum, the beta-arrestin-biased D2R caused a significant potentiation of amphetamine-ind

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

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

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

55 Therefore, we propose that betaarr2-biased D2R ligands that exert region-selective actions could pr

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

57 pound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold.

58 d characterization of novel G protein-biased D2R agonists.

59 ced locomotion, whereas the G protein-biased D2R had minimal effects.

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

61 Binding affinities at both D2R and D3R were higher when determined in competition w

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

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

64 eating phenotype may reflect altered central D2R function better than other commonly used obesity-rel

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

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

67 a-arrestin2- or limit G protein-dependent D1/D2R signaling could represent a more mechanistically inf

68 ctions of D1 and D2 dopamine receptors (D1R, D2R), the expression of which is largely separated betwe

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

70 ent findings where we failed to detect a D1R-D2R PLA signal in the adult striatum, in PD0 striatum we

71 proximity points to a possible role for D1R/D2R-mediated crosstalk in early striatal ontogeny.

72 cits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of t

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

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

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

76 nists behaved as A2AR agonists and decreased D2R function in the brain.

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

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

79 Mice lacking p11 in dopamine D2R-containing neurons have a reduced response to L-DOPA

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

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

82 Contrary to our expectation, D2R upregulation did not reduce alcohol intake during co

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

84 output pathway, which endogenously expresses D2Rs.

85 ng cAMP formation in cells singly expressing D2Rs but stimulating cAMP accumulation in D2R/NTS1R-coex

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

87 le and that G-protein signaling accounts for D2R canonical MAP kinase signaling cascade activation, w

88 but are simultaneously partial agonists for D2R/betaArr interactions.

89 ne and in complex with peptides derived from D2R and GRK1 reveals that the differential recognition i

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

91 s of alcoholic families suggesting that high D2R function may protect against alcohol dependence.

92 How D2R signals through the two pathways is still not well d

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

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

95 ng D2Rs but stimulating cAMP accumulation in D2R/NTS1R-coexpressing cells.

96 the role of G proteins and beta-arrestins in D2R signaling assays.

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

98 bserved persistence of cognitive deficits in D2R-OE mice.

99 There were no significant differences in D2R availability between obese and nonobese subjects in

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

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

102 ucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates.

103 or the altered activity of DA VTA neurons in D2R-OE mice: a reduction in the expression of distinct N

104 activity specifically in DMS D1R but not in D2R MSNs.

105 tein and beta-arrestin signaling pathways in D2R pharmacology, neurobiology, and associated pathologi

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

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

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

109 A possible protective role of increased D2R levels in the striatum is further supported by precl

110 higher BMI may be associated with increased D2R affinity in the VS.

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

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

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

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

115 ps and correlated with striatal and midbrain D2R binding.

116 Mimicking D2R signaling in iMSNs with Gi-DREADDs restored the leve

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

118 Moreover, D2R-blockade modulated similarity-based responses in the

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

120 Stimulating mPFC D2R+ neurons disrupts normal social interaction.

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

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

123 th precisely timed phasic stimulation of NAc D2R cells.

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

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

126 nally, we found that blockade of D1R but not D2R activity in the DMS attenuates alcohol consumption.

127 The selective ablation of D2R from cholinergic neurons allows discrimination betwe

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

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

130 efficacy of D2R agonists and the affinity of D2R antagonists.

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

132 dly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R

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

134 nuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agoni

135 Specifically, antagonism of D2R signaling by the typical antipsychotic haloperidol i

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

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

138 f antipsychotics is triggered by blockade of D2R on cholinergic interneurons and the consequent incre

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

140 e in support of intrastriatal connections of D2R(+)-MSNs (iMSNs) with dMSNs and indicate that D2R sig

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

142 We have developed ligands that are devoid of D2R-mediated G(i/o) protein signaling, but are simultane

143 rease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists.

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

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

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

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

148 mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neuron

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

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

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

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

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

154 ovides novel insight into the unique role of D2R-mediated neuronal activity to reward-associated cues

155 hese studies illuminate the critical role of D2R-mediated signaling in regulating the activity of str

156 A), but not in the substantia nigra (SN), of D2R-OE mice.

157 ase is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

158 Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress l

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

162 vioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning.

163 However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking

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

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

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

167 fashion, confirming that this ADP depends on D2Rs.

168 data demonstrate that p11 located in ChAT or D2R-containing neurons is involved in regulating therape

169 ss a fluorescence marker to visualize D1R or D2R MSNs, we show that repeated cycles of systemic admin

170 tetrahydroisoquinoline head group with other D2R "privileged structures" generated orthosteric antago

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

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

173 protective role of accumbal indirect pathway D2Rs in alcohol consumption but emphasize their importan

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

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

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

177 Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tigh

178 this, Evolutionary Trace was used to produce D2R mutants with strongly biased signal transduction for

179 differential effects of dopamine-2 receptor (D2R) and its agonist-induced activation on trafficking o

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

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

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

183 tudies have shown that dopamine D2 receptor (D2R) antagonism, paired with a motor task, not only impa

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

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

186 chlorperazine (PCZ), a dopamine D2 receptor (D2R) antagonist approved to treat nausea, vomiting, and

187 use many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly

188 or (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that

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

190 or learning induced by dopamine D2 receptor (D2R) blockade in mice.

191 tin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripip

192 ages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit t

193 e at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamin

194 in GPCR structure and dopamine D2 receptor (D2R) function.

195 The dopamine D2 receptor (D2R) has received much attention in obesity studies.

196 ne A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal

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

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

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

200 ned if these related to central D2 receptor (D2R) specific binding independent of BMI.

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

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

203 ne signals through the dopamine D2 receptor (D2R) to modulate central nervous system functions throug

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

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

206 oupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalization and surface express

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

208 f sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized.

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

210 t least in part, by elevated D2 DA receptor (D2R) expression and upregulated ERK1/2 activation.

211 e identified a key role of D2-like receptor (D2R)-expressing neurons in response to a reward-predicti

212 amine D2 receptor/neurotensin NTS1 receptor (D2R/NTS1R) heterodimers.

213 Striatal dopamine D2 receptors (D2R) are major regulators of motor activity through thei

214 sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity.

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

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

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

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

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

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

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

222 and reversibly overexpress DA D2 receptors (D2Rs) in the striatum (D2R-OE mice).

223 availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine in

224 Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhib

225 lthough partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneous

226 opamine D1 receptors (D1Rs) or D2 receptors (D2Rs), which drive "Go" or "No-Go" behaviors, respective

227 commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments rema

228 that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of

229 e exclusively a subset of D2-like receptors (D2Rs), whereas dopamine-mediated responses proximal to t

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

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

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

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

234 rception, striatal D2R BPND, and age-related D2R BPND declines.

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

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

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

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

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

240 onship between genetic ancestry and striatal D2R.

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

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

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

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

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

246 Conversely, high striatal D2R binding has been observed in unaffected members of a

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

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

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

250 Normalizing striatal D2R activity by switching off the transgene in adulthood

251 ed locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity.

252 es, sweetness intensity perception, striatal D2R BPND, and age-related D2R BPND declines.

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

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

255 ress DA D2 receptors (D2Rs) in the striatum (D2R-OE mice).

256 function of dopamine), our analysis suggests D2R as central player of either process.

257 first report of serum antibodies to surface D2R and NR1 in pediatric patients with isolated psychosi

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

259 D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons.

260 As anticipated, we found that D2R upregulation leads to hyperactivity in the open fiel

261 Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant

262 +)-MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of in

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

264 The results show that D2R interactions with the two downstream effectors are d

265 opaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the

266 We show that D2R signaling on cholinergic interneurons contributes to

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

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

269 ty and intrinsic efficacy of dopamine at the D2R.

270 -mediated beta-arrestin-2 recruitment at the D2R/NTS1R-coexpressing cells.

271 to a reward-predicting cue, whereas both the D2R and D1R types modulate responses of neurons proximal

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

273 modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle difference

274 negative cooperativity and affinity for the D2R.

275 We find that two copies of the D2R peptide bind within the hydrophobic crevice on Ca(2+

276 gonist quinpirole reversed the effect of the D2R.

277 act as negative allosteric modulators of the D2R.

278 These results indicate that the D2R is the primary DA D2-like receptor subtype mediating

279 tionnaires and underwent PET scans using the D2R-selective and nondisplaceable radioligand (N-[(11)C]

280 extracellular ends of TM2 and TM7 within the D2R protomer.

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

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

283 These findings indicate that DA, through D2R activation in iMSNs, regulates motor output by const

284 geting viral binding and viral entry through D2R- and clathrin-associated mechanisms, respectively.

285 ognition learning and memory in mice through D2Rs.

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

287 above the control mean, serum antibodies to D2R or NR1 were detected in 8 of 43 psychotic patients b

288 Positive immunoglobulin binding to D2R was found in 3 of 43 psychosis patients (3 IgG, 1 Ig

289 se between DA and radiotracer for binding to D2R.

290 t deletion blunted postsynaptic responses to D2R antagonism.

291 release and blunt postsynaptic responses to D2R antagonists.

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

293 of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variant

294 To this end, we upregulated D2R expression levels in the nucleus accumbens of the ad

295 l deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing functio

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

297 file: D3R Ki = 6.84 nM, 1700-fold D3R versus D2R binding selectivity, and its metabolic stability in

298 ng in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhi

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

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

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