Indices of dentate gyrus neurogenesis are unaffected immediately after or following withdrawal from morphine self-administration compared to saline self-administering control male rats

Sarah E. Bulin, Steven J. Simmons, Devon R. Richardson, Sarah E. Latchney, Hannah M. Deutsch, Sanghee Yun, Amelia J. Eisch

Research output: Contribution to journalArticle

Abstract

Opiates – including morphine – are powerful analgesics with high abuse potential. In rodents, chronic opiate exposure or self-administration negatively impacts hippocampal-dependent function, an effect perhaps due in part to the well-documented opiate-induced inhibition of dentate gyrus (DG) precursor proliferation and neurogenesis. Recently, however, intravenous (i.v.) morphine self-administration (MSA) was reported to enhance the survival of new rat DG neurons. To reconcile these disparate results, we used rat i.v. MSA to assess 1) whether a slightly-higher dose MSA paradigm also increases new DG neuron survival; 2) how MSA influences cells in different stages of DG neurogenesis, particularly maturation and survival; and 3) if MSA-induced changes in DG neurogenesis persist through a period of abstinence. To label basal levels of proliferation, rats received the S-phase marker bromodeoxyuridine (BrdU, i.p.) 24 -h prior to 21 days (D) of i.v. MSA or saline self-administration (SSA). Either immediately after SA (0-D) or after 4 weeks in the home cage (28-D withdrawal), stereology was used to quantify DG proliferating precursors (or cells in cell cycle; Ki67+ cells), neuroblast/immature neurons (DCX+ cells), and surviving DG granule cells (BrdU+ cells). Analysis revealed the number of DG cells immunopositive for these neurogenesis-relevant markers was similar between MSA and SSA rats at the 0-D or 28-D timepoints. These negative data highlight the impact experimental parameters, timepoint selection, and quantification approach have on neurogenesis results, and are discussed in the context of the large literature showing the negative impact of opiates on DG neurogenesis.

Original languageEnglish (US)
Article number112448
JournalBehavioural Brain Research
Volume381
DOIs
StatePublished - Mar 2 2020

Keywords

  • Addiction
  • BrdU
  • Doublecortin
  • Hippocampus
  • Ki67
  • Opiates
  • Proliferation

ASJC Scopus subject areas

  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Indices of dentate gyrus neurogenesis are unaffected immediately after or following withdrawal from morphine self-administration compared to saline self-administering control male rats'. Together they form a unique fingerprint.

  • Cite this