Retrieval of morphine-associated context induces cFos in dentate gyrus neurons

Phillip D. Rivera, Ramya K. Raghavan, Sanghee Yun, Sarah E. Latchney, Mary Katherin Mcgovern, Emily F. García, Shari G. Birnbaum, Amelia J. Eisch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Addiction has been proposed to emerge from associations between the drug and the reward-associated contexts. This associative learning has a cellular correlate, as there are more cFos+ neurons in the hippocampal dentate gyrus (DG) after psychostimulant conditioned place preference (CPP) versus saline controls. However, it is unknown whether morphine CPP leads to a similar DG activation, or whether DG activation is due to locomotion, handling, pharmacological effects, or-as data from contextual fear learning suggests-exposure to the drug-associated context. To explore this, we employed an unbiased, counterbalanced, and shortened CPP design that led to place preference and more DG cFos+ cells. Next, mice underwent morphine CPP but were then sequestered into the morphine-paired (conditioned stimulus+ [CS+]) or saline-paired (CS-) context on test day. Morphine-paired mice sequestered to CS+ had ∼30% more DG cFos+ cells than saline-paired mice. Furthermore, Bregma analysis revealed morphine-paired mice had more cFos+ cells in CS+ compared to CS- controls. Notably, there was no significant difference in DG cFos+ cell number after handling alone or after receiving morphine in home cage. Thus, retrieval of morphine-associated context is accompanied by activation of hippocampal DG granule cell neurons.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
Issue number4
StatePublished - Apr 1 2015


  • Addiction
  • Conditioned place preference
  • Hippocampus
  • Immediate early gene
  • Re-exposure

ASJC Scopus subject areas

  • Cognitive Neuroscience


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