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Neuropsychopharmacology. 2019 Jan;44(2):334-343. doi: 10.1038/s41386-018-0068-y. Epub 2018 Apr 17.

Opiate-associated contextual memory formation and retrieval are differentially modulated by dopamine D1 and D2 signaling in hippocampal-prefrontal connectivity.

Author information

1
College of Forensic Science, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China.
2
Intensive Care Unit, Shaanxi Provincial People's Hospital, 710061, Xi'an, Shaanxi, China.
3
Xi'an Mental Health Center, 710061, Xi'an, Shaanxi, China. bx32@drexel.edu.
4
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA. bx32@drexel.edu.

Abstract

Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories. Morphine-CPP acquisition increased the activity of the D1R-ERK-CREB pathway in both the vHip and mPFC. Morphine-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the vHip and PFC. Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are required for the acquisition and retrieval of the morphine contextual memory, respectively. Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spatial memory. These results suggest that D1R and D2R signaling are differentially involved in the acquisition and retrieval of morphine contextual memory, and DA signaling in the vHip-mPFC connection contributes to morphine-associated and normal memory, largely depending on opiate exposure states.

PMID:
29728647
PMCID:
PMC6300561
DOI:
10.1038/s41386-018-0068-y
[Indexed for MEDLINE]
Free PMC Article

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