Up-regulation of dopamine D1 receptor in the hippocampus after establishment of conditioned place preference by cocaine

2011 ◽  
Vol 61 (4) ◽  
pp. 842-848 ◽  
Author(s):  
Tomoko Tanaka ◽  
Nobuyuki Kai ◽  
Kazuto Kobayashi ◽  
Yuji Takano ◽  
Naoyuki Hironaka
Keyword(s):  
Conditioned Place Preference ◽  
Place Preference ◽  
Dopamine D1 Receptor ◽  
D1 Receptor

scholarly journals Cocaine-dependent acquisition of locomotor sensitization and conditioned place preference requires D1 dopaminergic signaling through a cyclic AMP, NCS-Rapgef2, ERK and Egr-1/Zif268 pathway

2020 ◽  
Author(s):  
Sunny Zhihong Jiang ◽  
Sean Sweat ◽  
Sam Dahlke ◽  
Kathleen Loane ◽  
Gunner Drossel ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Conditioned Place Preference ◽  
Mouse Brain ◽  
Place Preference ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Locomotor Sensitization ◽  
Erk Activation ◽  
Erk Phosphorylation ◽  
Dopamine Signaling

ABSTRACTElucidation of the underlying mechanism of dopamine signaling to ERK that underlies plasticity in dopamine D1 receptor expressingneurons leadingto acquired cocaine preference is incomplete. NCS-Rapgef2 is a novel cAMP effector, expressed in neuronal and endocrine cells in adult mammals, that is required for D1 dopamine receptor-dependent ERK phosphorylation in mouse brain. In this report, we studied the effects of abrogating NCS-Rapgef2 expression on cAMP-dependent ERK→Egr-1/zif268 signaling in cultured neuroendocrine cells; in D1 medium spiny neurons (MSNs) of nucleus accumbens slices; and in mouse brain in a region-specific manner. NCS-Rapgef2 gene deletion in the nucleus accumbens (NAc) in adult mice, using AAV-mediated expression of cre recombinase, eliminated cocaine-induced ERK phosphorylation and Egr-1/Zif268 upregulation in D1-MSNs and cocaine-induced behaviors including locomotor sensitization and conditioned place preference (CPP). Abrogation of NCS-Rapgef2 gene expression in medium prefrontal cortex and basolateral amygdala, by crossing mice bearing a floxed Rapgef2 allele with a cre mouse line driven by calcium/calmodulin-dependent kinase IIα promoter also eliminated cocaine-induced phospho-ERK activation and Egr-1/Zif268 induction, but without effect on the cocaine-induced behaviors. Our results indicate that NCS-Rapgef2 signaling to ERK in dopamine D1-receptor expressing neurons in the NAc, butnotin corticolimbic areas, contributes to cocaine-induced locomotor sensitization and CPP. Ablation of cocaine-dependent ERK activation by elimination of NCS-Rapgef2 occurred with no effect on phosphorylation of CREB in D1 dopaminoceptive neurons of NAc. This study reveals a new cAMP-dependent signaling pathway for cocaine-induced behavioral adaptations, mediated through NCS-Rapgef2/phospho-ERK activation, independently of PKA/CREB signaling.SIGNIFICANCE STATEMENTERK phosphorylation in dopamine D1 receptor expressing neurons exerts a pivotal role in psychostimulant-induced neuronal gene regulation and behavioraladaptation, including locomotor sensitization and drug preference in rodents. In this study, we examined the role of dopamine signaling through the D1 receptor via a novel pathway initiated through the cAMP-activated guanine nucleotide exchange factor NCS-Rapgef2 in mice. NCS-Rapgef2 in the nucleus accumbens is required for activation of ERK and Egr-1/Zif268 in D1 dopaminoceptive neurons after acute cocaine administration, and subsequentenhanced locomotor response anddrugseeking behavior after repeated cocaine administration. This novel component in dopamine signaling provides a potential new target for intervention in psychostimulant-shaped behaviors, and new understanding of how D1-MSNs encode the experience of psychomotor stimulant exposure.

Retained cocaine conditioned place preference in D1 receptor deficient mice

Neuroreport ◽  
1995 ◽  
Vol 6 (17) ◽  
pp. 2314-2316 ◽  
Author(s):  
Lucinda L. Miner ◽  
John Drago ◽  
Paul M. Chamberlain ◽  
David Donovan ◽  
George R. Uhl
Keyword(s):  
Conditioned Place Preference ◽  
Place Preference ◽  
D1 Receptor ◽  
Deficient Mice

Downregulation of thioredoxin-1 in the ventral tegmental area delays extinction of methamphetamine-induced conditioned place preference

2018 ◽  
Vol 32 (9) ◽  
pp. 1037-1046
Author(s):  
Mengbing Huang ◽  
Ming Bai ◽  
Zhimin Zhang ◽  
Lu Ge ◽  
Kang Lu ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Conditioned Place Preference ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Place Preference ◽  
D1 Receptor ◽  
Element Binding Protein ◽  
Thioredoxin 1 ◽  
Ventral Tegmental ◽  
Extracellular Regulated Kinase

Background: Drug addiction is characterized by compulsive drug use and relapse. Thioredoxin-1 is emerging as an important modulator involved in the cellular protective response against a variety of toxic stressors. Previous study has reported that thioredoxin-1 overexpression prevents the acquisition of methamphetamine-conditioned place preference. Here, we aimed to investigate the effect of thioredoxin-1 on methamphetamine-conditioned place preference extinction and the possible mechanism. Methods: (a) An extinction procedure in mice was employed to investigate the effect of thioredoxin-1 on the extinction of methamphetamine-conditioned place preference. After the acquisition of methamphetamine-conditioned place preference, mice underwent the following procedures: the injection of thioredoxin-1 small interfering RNA in the ventral tegmental area followed by the post-conditioned place preference test, four days of extinction training followed by four days of recovery after surgery. (b) The levels of thioredoxin-1, dopamine D1 receptor, tyrosine hydroxylase, phosphorylated extracellular regulated kinase, and phosphorylated cyclic adenosine monophosphate response element binding protein were examined by using Western blot analysis. Results: Thioredoxin-1 downregulation in the ventral tegmental area delayed methamphetamine-conditioned place preference extinction. The expression of thioredoxin-1 was decreased in the ventral tegmental area of mice in control and negative groups after methamphetamine-conditioned place preference extinction, but not in the thioredoxin-1 siRNA group. The levels of dopamine D1 receptor, tyrosine hydroxylase, phosphorylated extracellular regulated kinase, and phosphorylated cyclic adenosine monophosphate response element binding protein were decreased in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of mice in the control and negative groups after methamphetamine-conditioned place preference extinction, but were inversely increased in thioredoxin-1 siRNA group. Conclusions: The results suggest that downregulation of thioredoxin-1 in the ventral tegmental area may delay methamphetamine-conditioned place preference extinction by regulating the mesocorticolimbic dopaminergic signaling pathway.

Upregulation of CCL7 and CCL2 in reward system mediated through dopamine D1 receptor signaling underlies methamphetamine-induced place preference in mice

2018 ◽  
Vol 665 ◽  
pp. 33-37 ◽  
Author(s):  
Fumihiro Saika ◽  
Norikazu Kiguchi ◽  
Naoki Wakida ◽  
Daichi Kobayashi ◽  
Yohji Fukazawa ◽  
...  
Keyword(s):  
Reward System ◽  
Place Preference ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Receptor Signaling
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