Protein Kinase D1-Dependent Phosphorylation of Dopamine D1 Receptor Regulates Cocaine-Induced Behavioral Responses

Wang, Ning; Su, Ping; Zhang, Ying; Lu, Jie; Xing, Bao Cai; Kang, Kai-Hsiang; Li, Wenqi; Wang, Yun

doi:10.1038/npp.2013.341

Cited by 21 publications

(24 citation statements)

References 48 publications

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“…24 hours after the last conditioning session, rats were tested following the same procedure as the preconditioning test (post-conditioning phase). The time spent in each chamber was recorded and CPP was determine by calculating a CPP score (time in paired chamber – time in unpaired chamber (Lax, George, Ignatz, & Kolber, 2014; Wang et al, 2014; Xue et al, 2014)).…”

Section: Methodsmentioning

confidence: 99%

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

Velázquez-Sánchez¹,

Santos²,

Smith³

et al. 2015

Behavioral Neuroscience

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Binge eating disorder is characterized by excessive consumption of highly palatable food within short periods of time accompanied by loss of control over eating. Extensive evidence provides support for the consideration of binge eating disorder as an addiction-like disorder. In this study, we wanted to determine whether rats undergoing an operant binge-like eating procedure could develop maladaptive forms of conditioned feeding behaviors. For this purpose, we trained male rats to self-administer either a sugary, highly palatable diet (Palatable rats) or a chow diet (Chow rats) for 1 hour a day. Following escalation and stabilization of palatable food intake, we tested Chow and Palatable rats in i) a conditioned place preference test, ii) a second-order schedule of reinforcement, and iii) a cue-induced suppression of feeding test. In the conditioned place preference task, Palatable rats spent significantly more time in the compartment that was previously paired with the palatable food, compared to Chow controls. Furthermore, in the second order schedule of reinforcement task, Palatable rats exhibited active lever responding 4- to 6-fold higher than Chow control rats. Finally, in the cue-induced suppression of feeding test, while Chow control subjects reduced responding by 32% in the presence of the conditioned punishment, Palatable rats persevered in responding despite the aversive cue. These results further characterize this animal model of binge-like eating and provide additional evidence for the addictive properties of highly palatable food.

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Section: Methodsmentioning

confidence: 99%

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

Velázquez-Sánchez¹,

Santos²,

Smith³

et al. 2015

Behavioral Neuroscience

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“…Cells were used 24 h post-transfection. YFP-D1R and YFP-S421A-D1R plasmids were described previously [9] .…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Thus, the heterotopic expression of S421A Our recent studies indicated that phosphorylation of the D1R at S421 promotes receptor membrane localization [9] , so we compared the levels of D1R localized in the membrane fractions in the striatum of WT and Tg-S421A mice. The membrane localization of D1R was reduced in Tg-S421A mice compared with WT mice (P <0.05, Fig.…”

Section: Reduced Membrane Localization and Downstream Erk Signaling Omentioning

confidence: 99%

“…PKD1, a relatively new member of the CaMK family, plays an important role in neuronal development, neuroprotection, and learning [28] . Recently, we revealed the critical role of PKD1 in cocaine addiction through phosphorylating S421 of the D1R [9] . Lentivirus-mediated PKD1 knockdown effectively reduced the increase in locomotor activity after acute cocaine injection.…”

Section: Attenuation Of Cocaine Cpp In Tg-s421a Micementioning

confidence: 99%

“…Our recent studies revealed a new protein kinase, protein kinase D1 (PKD1), which is involved in D1R phosphorylation [9] . In contrast to the down-regulation of D1R function by GRK-, PKA-, or PKC-mediated phosphorylation, PKD1-mediated phosphorylation of the D1R at S421 promotes the membrane localization of D1Rs and contributes to the behavioral effects of cocaine.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice

Zhang

Wang

et al. 2014

Neurosci. Bull.

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Dopamine D1 receptors (D1Rs) play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1R in the forebrain. These transgenic mice showed reduced phospho-D1R (S421) and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These fi ndings provide in vivo evidence for the critical role of S421 phosphorylation of the D1R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders.

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Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

et al. 2016

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Caffeine is the world’s most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

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Protein Kinase D1-Dependent Phosphorylation of Dopamine D1 Receptor Regulates Cocaine-Induced Behavioral Responses

Cited by 21 publications

References 48 publications

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice

Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

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