ライフサイエンスコーパス: cocaine

1 nce the structure of NAc MSNs in response to cocaine.

2 e cue when it predicts impending but delayed cocaine.

3 gonists decreased abuse-related behaviors of cocaine.

4 et an attenuated locomotor response to acute cocaine.

5 the notion that alcohol is a gateway drug to cocaine.

6 avioral effects of drugs of abuse, including cocaine.

7 f cocaine seeking in mice self-administering cocaine.

8 ions affect genes that regulate responses to cocaine.

9 and in the rewarding effects of alcohol and cocaine.

10 VTA, and this effect enhances motivation for cocaine.

11 hat have a role in modulating motivation for cocaine.

12 sition from moderate to compulsive intake of cocaine.

13 profiles and alternative splicing induced by cocaine.

14 ochondria in D1-MSN dendrites after repeated cocaine.

15 significantly lower addictive potential than cocaine.

16 e consumption or the reinforcing efficacy of cocaine.

17 nces seeking after long-term abstinence from cocaine.

18 tial therapeutic utility in the treatment of cocaine abuse.

19 long-lasting, and persist following extended cocaine access.

20 ection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiot

21 Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifi

22 2F3a as a novel transcriptional regulator of cocaine action in NAc.

23 However, the role of PGC-1alpha in NAc in cocaine action is unknown.

24 strate a novel role for PGC-1alpha in NAc in cocaine action.

25 subjective effects is a cardinal symptom of cocaine addiction and a DSM-V criterion for substance ab

26 ed at these complexes may have potential for cocaine addiction treatment.SIGNIFICANCE STATEMENT Toler

27 peractivity disorder, binge eating disorder, cocaine addiction, obesity, and type 2 diabetes.

28 bits is not necessary for the development of cocaine addiction-like behavior in rats.SIGNIFICANCE STA

29 f opiate and nicotine addiction, but not for cocaine addiction.

30 support a personalized treatment approach to cocaine addiction.

31 produce substantial adverse consequences for cocaine addiction.

32 e their potential pathophysiological role in cocaine addiction.

33 e social-emotional functional alterations in cocaine addiction.

34 ay have translational potential for treating cocaine addiction.

35 s increase the risk of relapse in recovering cocaine addicts are not well understood.

36 Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerabilit

37 ortem in the nucleus accumbens of male human cocaine addicts.

38 However, to procure such drugs as cocaine, addicts often require considerable ingenuity an

39 ed locomotor activation in response to acute cocaine administration and an altered locomotor sensitiz

40 -E2F3a and E2F3b-in mouse NAc after repeated cocaine administration and assayed the effects of overex

41 After chronic cocaine administration and following withdrawal, an acut

42 inguished preference in response to low-dose cocaine administration did not differ between genotypes.

43 dopamine signaling in the striatum by acute cocaine administration reveals that absence of D2L, but

44 n response to early withdrawal from repeated cocaine administration, de novo dendritic spine formatio

45 med on SPNs 1 hour and 1 week after a single cocaine administration.

46 G9a in nucleus accumbens (NAc) after chronic cocaine administration.

47 aine intake while ignoring their alternative cocaine alone option.

48 Early withdrawal from repeated cocaine also produces dramatic alterations in the transc

49 t toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons.

50 is a target for addictive compounds such as cocaine, amphetamine (AMPH), and methamphetamine (METH).

51 Fasudil also blocks habitual responding for cocaine, an effect that persists over time, across multi

52 DAT is the target for psychostimulants-like cocaine and amphetamine-and plays an important role in n

53 locker Naspm into the NAc shell reversed the cocaine and depressive-like phenotypes.

54 in the abstinence/saline condition vs acute cocaine and HC.

55 uman laboratory studies to date, craving for cocaine and heroin is greater with the combination of dr

56 HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-sali

57 s for approximately 1 week after terminating cocaine and is accompanied by an increased susceptibilit

58 nd compared the effects of the DAT inhibitor cocaine and its fluorescent analog JHC1-64 on the plasma

59 Here, we show that stimulants like cocaine and methamphetamine greatly increase HS content

60 of PLCgamma1 both reduces the motivation for cocaine and reverses dendritic spine density, suggesting

61 r fixed and progressive ratio responding for cocaine and stress-induced reinstatement of drug-seeking

62 tory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific a

63 terial smooth muscle cells on treatment with cocaine and Tat.

64 status influences the reinforcing effects of cocaine and the effects of some drugs on cocaine self-ad

65 Exposure to cocaine and the test chamber induced rapid and transient

66 xcitatory SNc afferent nuclei in response to cocaine, and suggest a compelling architecture for diffe

67 In contrast to the cocaine- and depression-related phenotypes, GluA1/A2 AMP

68 unolabeled neurons of VTA, but did attenuate cocaine- and orexin-induced increases in calcium transie

69 uitry that drives addiction and relapse, yet cocaine apparently has no effect on electrically stimula

70 rganoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation o

71 ncement in the motivation to self-administer cocaine as measured using a progressive ratio reinforcem

72 s effect of LHb inhibition was selective for cocaine, as it did not impair responding for sucrose rei

73 Notably, animals with cocaine-associated alterations in dopamine signals for r

74 32476 inhibited cocaine self-administration, cocaine-associated cue-induced relapse to drug seeking,

75 1 receptor-expressing cells in extinction of cocaine-associated memories, providing a framework for f

76 cocaine-evoked plasticity and/or disrupt the cocaine-associated memory.

77 effects of rewarding drugs via regulation of cocaine-associated stimuli.

78 Molecules critically involved in cocaine behavioral plasticity are known to regulate and

79 sion or depletion of E2f3 isoforms in NAc on cocaine behavioral responses.

80 Cocaine binding significantly increased the density of R

81 -seeking behavior likely by interfering with cocaine binding to DAT.

82 second alternative porthole earned identical cocaine but without ChR2 stimulation.

83 e density along with enhanced motivation for cocaine, but a functional relationship between these mor

84 However, an acute exposure to cocaine can trigger long-lasting synaptic plasticity in

85 ether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco.

86 istration and following withdrawal, an acute cocaine challenge induced WAVE1 activation in striatum,

87 ay) doses also failed to significantly alter cocaine choice.

88 red color in the test line indicate that the cocaine concentrations were analyzed via a smartphone ap

89 adeno-associated virus and Cre lines during cocaine conditioned place preference and cocaine-induced

90 on of Npas4 in the NAc significantly reduced cocaine conditioned place preference and delayed learnin

91 Using a cocaine-conditioned locomotion (CL) procedure, the prese

92 the role of NAc silent synapse maturation in cocaine-conditioned place preference (CPP).

93 (shell)), and dorsal striatum (DS) following cocaine conditioning and EXT in Fos-GFP mice that expres

94 or uptake tracked individual differences in cocaine consumption or the reinforcing efficacy of cocai

95 e cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-re

96 -expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent

97 ld-type and knockout mice alike all acquired cocaine-CPP and exhibited increased levels of silent syn

98 s not required for establishing or retaining cocaine-CPP.

99 tivity correlated negatively with ratings of cocaine craving and positively with how high subjects fe

100 ations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that

101 intensification (incubation) of cue-induced cocaine craving has been demonstrated after withdrawal f

102 ng-lasting changes in subsequent measures of cocaine craving/relapse.

103 importance of social-emotional functions in cocaine dependence, and provides a potential underlying

104 -related variability in reward processing in cocaine-dependent individuals (CD) is not well understoo

105 ndent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30

106 Cocaine-dependent variability in outcome- and loss-magni

107 Here we present a potentiometric sensor for cocaine detection based on molecularly imprinted polymer

108 cle cells on exposure to HIV-proteins and/or cocaine due to severe down-modulation of bone morphogene

109 Rats were trained to self-administer cocaine, during which time each active lever press resul

110 administration in rats, we link tolerance to cocaine effects at the dopamine transporter (DAT) with a

111 ted cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbe

112 during memory reactivation would reverse the cocaine-evoked plasticity and/or disrupt the cocaine-ass

113 Taken together, these data reveal that cocaine-evoked synaptic plasticity in PL-mPFC is reversi

114 This rule change is caused by cocaine-exacerbated D1-cAMP/protein kinase A dopamine si

115 h its diverse pathophysiological mechanisms, cocaine exerts various adverse effects on the cardiovasc

116 In a group of cocaine-experienced male cynomolgus monkeys (N=4), THC S

117 show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and

118 l correlates in DLS are affected by previous cocaine exposure as rats performed a complex reward-guid

119 ese findings are intriguing because repeated cocaine exposure decreases G9a in this region and thereb

120 Cocaine exposure disrupted the balance between excitatio

121 Surprisingly, we found that previous cocaine exposure enhanced R-O associations in DLS.

122 rious neurodevelopmental effects of prenatal cocaine exposure in humans.

123 These results suggest that repeated cocaine exposure in vivo disrupts the balance between ex

124 Here, we show that repeated cocaine exposure in vivo does not alter synaptic strengt

125 support of this idea, we found that repeated cocaine exposure led to an increase in the single-unit a

126 Following a single in vivo cocaine exposure, the desensitization of D2 receptors fr

127 for synaptic modifications following in vivo cocaine exposure.

128 c following E2f3a overexpression or repeated cocaine exposure.

129 is demonstrated on the crystal structures of cocaine, flutamide, flufenamic acid, the K salt of penic

130 social pen; 30 min later he was studied in a cocaine-food choice paradigm.

131 ction and may be motivated to continue using cocaine for reasons beyond desired drug-related effects.

132 inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not

133 Here, the cocaine group exhibited a small leftward shift in the di

134 d NOP (-/-) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the

135 human metabolites of mephedrone, methadone, cocaine, heroin, codeine, and tetrahydrocannabinol (THC)

136 ing and memory, autism, and sensitization to cocaine; however, the mechanism is not known.

137 ll as increased responding for and intake of cocaine in an intravenous self-administration test.

138 le also modulating the reinforcing effect of cocaine in an operant-based self-administration task.

139 in IC50 for inhibition of [(3)H]DA uptake by cocaine in WT hDAT.

140 However, cocaine increased DAT exit from retromer-positive endoso

141 We demonstrated that cocaine increased GPe neuron activity, which accounted f

142 previously found that self-administration of cocaine increases AMPA glutamate receptors in the VTA, a

143 lutamate spillover in the NAcore would mimic cocaine-induced adaptations and potentiate cued reinstat

144 Moreover, riluzole reversed bidirectional cocaine-induced adaptations in intrinsic excitability of

145 (E2F3) as a prominent upstream regulator of cocaine-induced changes in gene expression and alternati

146 Resveratrol pretreatments attenuated cocaine-induced conditioned place preference and blocked

147 These mice, however, showed unaltered cocaine-induced conditioned place preference.

148 e interacting kinase-1 has a pivotal role in cocaine-induced connectivity.

149 xcitability was decreased by riluzole, and a cocaine-induced decrease in IL excitability was increase

150 ppression of cocaine-seeking and reversal of cocaine-induced dephosphorylation of key phosphoproteins

151 It also unravels a new functional role for cocaine-induced extracellular signal-regulated kinase pa

152 L) and infralimbic (IL) pyramidal neurons; a cocaine-induced increase in PL excitability was decrease

153 s basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopami

154 ing cocaine conditioned place preference and cocaine-induced locomotion.

155 d locomotor activity, but markedly increased cocaine-induced locomotion.

156 pression or knockdown in mouse NAc regulates cocaine-induced locomotor and place conditioning behavio

157 ively in dopamine neurons exhibit heightened cocaine-induced locomotor responses.

158 ibitory effects of peripheral stimulation on cocaine-induced neuronal activation in the nucleus accum

159 thermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3

160 either the D2S or D2L variant to investigate cocaine-induced plasticity in D2 receptor signaling.

161 conditioned place preference and blocked the cocaine-induced reduction of GABAergic inhibition in VTA

162 We propose that a cocaine-induced shift from MRN-driven serotonergic contr

163 This cocaine-induced, extended-timing t-LTP lasts for approxi

164 Here we show that cocaine induces alterations in nuclear F-actin signaling

165 Repeated exposure to cocaine induces lasting epigenetic changes in neurons th

166 Cocaine induces the rapid induction of Arc and its nucle

167 each active lever press resulted in an i.v. cocaine infusion paired with one of two cues that altern

168 During conditioning, mice received repeated cocaine injections (20 mg/kg) paired with a locomotor ac

169 After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons i

170 ontrast, SERT knockdown in the DRN increased cocaine intake selectively under LgA conditions and, lik

171 option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine

172 ion of oligomers is concomitant with reduced cocaine intake, and propose that pharmacotherapeutics ai

173 Cocaine is the leading cause for drug-abuse-related visi

174 binding to DAT, but they themselves are not cocaine-like.

175 b lesions reversed the inhibitory effects on cocaine locomotion produced by peripheral stimulation.

176 cocaine on dendritic spine formation and for cocaine-mediated behavioral sensitization.

177 nd attenuate the effects of SRI-compounds on cocaine-mediated dissociation rate.

178 Rats were trained to self-administer cocaine (n = 96) or were used as yoked-saline control an

179 luating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as c

180 88F hDAT potentiate the inhibitory effect of cocaine on DA uptake and attenuate the effects of SRI-co

181 ion, in turn, is critical for the effects of cocaine on dendritic spine formation and for cocaine-med

182 The relative impact of chronic vs acute cocaine on dependence-related variability in reward proc

183 se data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consu

184 now we demonstrate the effect of HIV-Tat and cocaine on the proliferative TGF-beta signaling cascade.

185 quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating coca

186 s attenuates reinstatement induced by either cocaine or a D1DR agonist.

187 r bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the mos

188 oaches with behavioral paradigms relevant to cocaine phenotypes.

189 g patch clamp electrophysiology we find that cocaine place conditioning increases excitatory presynap

190 ing within the same procedure, and find that cocaine potency at the DAT also tracks differences in pe

191 s later reactivated with either i.v. or i.p. cocaine presentation in the absence of any cue.

192 e hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3.

193 icosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-

194 level corticosterone treatment to potentiate cocaine-primed reinstatement was recapitulated by intra-

195 eftward shift in the dose-response curve for cocaine-primed reinstatement.

196 ent in response to an otherwise subthreshold cocaine priming dose (2.5 mg/kg, intraperitoneal).

197 or during punishment-induced suppression of cocaine-reinforced responding.

198 llowing social confrontation, sensitivity to cocaine reinforcement was significantly greater in subor

199 asic understanding of DATs and their role in cocaine reinforcement, we serendipitously identified a n

200 Here we examine the role of AKAP150 in cocaine reinstatement, an animal model of relapse.

201 DAC5) in the nucleus accumbens (NAc) reduced cocaine reward-context associations and relapse-like beh

202 neurons demonstrated that both genes promote cocaine reward.

203 des insight into the molecular mechanisms of cocaine's contribution to key components in HIV pathogen

204 NAc MSNs, but how such alterations influence cocaine's effects on dendritic spine formation remain un

205 reatment.SIGNIFICANCE STATEMENT Tolerance to cocaine's subjective effects is a cardinal symptom of co

206 bolstered by the extensive recapitulation of cocaine's transcriptional effects in NAc by overexpressi

207 es an enduring postexpression enhancement in cocaine SA and prolonged (over 5 weeks) increases in rei

208 expression is limited to the initial 15 d of cocaine SA training, it produces an enduring postexpress

209 he LHb with GABAergic agonists did not alter cocaine SA under progressive ratio or seeking/taking cha

210 infusion of BDNF into the PrL cortex blocked cocaine SA-induced dephosphorylation of ERK, GluN2A, and

211 xone to prevent cue-induced reinstatement of cocaine seeking and normalize glutamatergic proteins in

212 and that HS contributes to the regulation of cocaine seeking and taking.

213 DynA blocked OrxA-induced cocaine seeking but not SCM seeking.

214 ental response during extinction learning of cocaine seeking encodes information required for such le

215 el corticosterone treatment alone reinstates cocaine seeking following self-administration and extinc

216 N cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration

217 also mitigated cue-induced reinstatement of cocaine seeking in mice self-administering cocaine.

218 (over 5 weeks) increases in reinstatement of cocaine seeking induced by foot-shock stress, but in the

219 ratio reinforcement schedule and to enhanced cocaine seeking measured in extinction/reinstatement tes

220 discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that th

221 DRs) in the nucleus accumbens shell promoted cocaine seeking through a process involving the activati

222 Reinstatement of cocaine seeking was then tested after footshock exposure

223 l corticosterone on PL neurotransmission and cocaine seeking were determined using intra-PL microinfu

224 In contrast, LHb inhibition increased cocaine seeking when the drug was not available in rats

225 ceftriaxone attenuates the reinstatement of cocaine seeking while increasing the function of the glu

226 nNOS-expressing interneurons in cue-induced cocaine seeking, revealing a bottleneck in brain process

227 ritical for the cue-induced reinstatement of cocaine seeking, which may be mediated by mTORC1 and ERK

228 fficient for stress-induced reinstatement of cocaine seeking.

229 in the nucleus accumbens (NAc) in relapse to cocaine seeking.

230 e influence of D1 inputs to drive relapse to cocaine seeking.

231 romoted the subsequent cued reinstatement of cocaine seeking.

232 n cocaine self-administration and relapse to cocaine seeking.

233 ccumbens in the neural mechanisms underlying cocaine seeking.

234 se-context- and cue-induced reinstatement of cocaine seeking.

235 ransient synaptic potentiation and reinstate cocaine seeking.

236 s necessary for BDNF-mediated suppression of cocaine-seeking and reversal of cocaine-induced dephosph

237 hat exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k p

238 NorBNI did not induce or potentiate cocaine-seeking behavior induced by OrxA but reversed Dy

239 16 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by interfering with coca

240 tween these brain regions mediate CS-induced cocaine-seeking behavior.

241 ction learning and the active suppression of cocaine-seeking behavior.

242 ation of mechanisms underlying extinction of cocaine-seeking behavior.

243 es to cue- and drug-induced reinstatement of cocaine-seeking behavior.

244 ich involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechani

245 paORs governs the prolonged reinstatement to cocaine-seeking observed after cold water swim stress.

246 re and shell inhibited cue- and drug-induced cocaine-seeking, respectively.

247 euroadaptations in reward circuits following cocaine self-administration (SA) underlie reinstatement

248 ombined a behavioral economics approach with cocaine self-administration and ex vivo voltammetric rec

249 oxicating levels of alcohol had no effect on cocaine self-administration and relapse to cocaine seeki

250 ared to the control, significantly decreased cocaine self-administration by 67% relative to baseline

251 Cocaine self-administration elevated BNST PACAP, and BNS

252 We examined the impact that prior cocaine self-administration had on firing in dorsal late

253 Using cocaine self-administration in rats, we link tolerance t

254 associations and relapse-like behaviors in a cocaine self-administration model.

255 In a substitution test, cocaine self-administration rats displayed a progressive

256 ting wild-type TrkB expression after chronic cocaine self-administration reverses the sustained incre

257 These results suggest that cocaine self-administration strengthens action-outcome e

258 two phases of relapse after extinction from cocaine self-administration to assess how cocaine use af

259 Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaine-associated cue-indu

260 Alcohol pre-exposure had no effect on cocaine self-administration, extinction responding, and

261 lectively under LgA conditions and, like LgA cocaine self-administration, reduced CRF immunodensity i

262 of Drp1 in D1-MSNs blocks drug seeking after cocaine self-administration, while enhancing the fission

263 earning of the drug-reinforced action during cocaine self-administration, without affecting cue-induc

264 tion in rats and monkeys, but did not affect cocaine self-administration.

265 of cocaine and the effects of some drugs on cocaine self-administration.

266 behavior, as did withdrawal from ShA or LgA cocaine self-administration.

267 mission in vivo expedited the acquisition of cocaine self-administration.

268 have divergent effects on brain function and cocaine self-administration.

269 downregulated in the NAcsh of rats following cocaine self-administration.

270 identified SNc inputs and determine whether cocaine sensitivity in the mouse SNc circuit is conferre

271 acute locomotor response to amphetamine and cocaine similarly depend on both G-protein and beta-arre

272 n dopamine signaling and discrete aspects of cocaine taking and seeking.

273 eatment with JJC8-016 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by in

274 the dopamine transporter (DAT) with aberrant cocaine-taking behaviors.

275 f HCRT in the persistence of compulsive-like cocaine-taking has yet to be fully elucidated.

276 prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibit

277 In the presence of cocaine, the rate of spontaneous dopamine transients was

278 transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by e

279 nance energy transfer imaging, we found that cocaine tolerance is associated with the formation of DA

280 ntracellular trafficking studies of HIV-1 in cocaine treated DCs revealed increased co-localization o

281 icking and decreased degradation of HIV-1 in cocaine treated DCs.

282 revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in pa

283 om cocaine self-administration to assess how cocaine use affects t-SP associated with cue-induced dru

284 ts alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

285 al profiles and potential for development as cocaine use disorder therapeutics.

286 The development of medications to treat cocaine use disorders has thus far defied success, leavi

287 Cocaine use during adolescence increases vulnerability t

288 Animal models indicate that chronic cocaine use enhances excitatory glutamatergic input to t

289 We found that cocaine use for 10 minutes collapsed all three measures

290 SIGNIFICANCE STATEMENT: Relapse to cocaine use in a rat model is associated with transient

291 Chronic cocaine use is associated with prominent morphological c

292 ating the durable consequences of early-life cocaine use may benefit from targeting cytoskeletal regu

293 instatement paradigm, we show that achieving cocaine use reversed the synaptic plasticity underpinnin

294 ts suggest that rather than directly driving cocaine use, stress may create a biological context with

295 n important determinant of susceptibility to cocaine use.

296 Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects a

297 t robust reduction observed to date in human cocaine users and the first to involve mechanisms other

298 in MSN subtypes was assessed after repeated cocaine using D1-Cre-RiboTag and D2-Cre-RiboTag lines.

299 tempers the locomotor stimulatory effect of cocaine while also modulating the reinforcing effect of

300 fects of SRI-compounds on the interaction of cocaine with hDAT.