title: Retrieval of morphine-associated context induces cFos in dentate gyrus neurons.
abstract: 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.
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Rivera
authors.forename: Ramya K
authors.initials: RK
authors.lastname: Raghavan
authors.forename: Sanghee
authors.initials: S
authors.lastname: Yun
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Latchney
authors.forename: Mary-Katherin
authors.initials: MK
authors.lastname: McGovern
authors.forename: Emily F
authors.initials: EF
authors.lastname: García
authors.forename: Shari G
authors.initials: SG
authors.lastname: Birnbaum
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Eisch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D011939:Mental Recall / Q000187:drug effects*; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine
keywords: addiction; conditioned place preference; hippocampus; immediate early gene; re-exposure