title: The opiate analgesic buprenorphine decreases proliferation of adult hippocampal neuroblasts and increases survival of their progeny.
abstract: Although opiate drugs of abuse have been shown to decrease adult hippocampal neurogenesis, the impact of opiate analgesics has not been tested. North American regulatory boards governing the ethical treatment of experimental animals require the administration of analgesics, such as buprenorphine, following minor surgical interventions. Here, we show that two commonly used post-operative buprenorphine dosing regimes significantly inhibit the proliferation of doublecortin-positive neuroblasts but not other hippocampal stem and progenitor cell populations in adult mice. Buprenorphine, administered in schedules of three 0.05 mg/kg subcutaneous injections over a single day or seven 0.05 mg/kg injections over a 3-day period decreased the number of actively proliferating 5-iodo-2'-deoxyuridine-labeled doublecortin-positive cells for up to 6 days after opiate withdrawal. The minimal (three injection), but not standard (seven injection), analgesic paradigm also reduced basal indices of hippocampal progenitor cell apoptosis and enhanced survival of newly born cells for up to 28 days. Taken together, these data provide the first evidence that the routine administration of opiate analgesics has transient but long-lasting effects on neurogenesis and further emphasize that analgesic dosage and schedule should be reported and considered when interpreting the magnitude of neural stem and progenitor cell activation in response to in vivo intervention.
authors.affiliation: Neural Regeneration Laboratory and Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada.
authors.forename: A S
authors.initials: AS
authors.lastname: Pettit
authors.forename: R
authors.initials: R
authors.lastname: Desroches
authors.forename: S A L
authors.initials: SA
authors.lastname: Bennett
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects*; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002047:Buprenorphine / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003857:Deoxyuridine / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009457:Neuroglia / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000700:Analgesics; D000941:Antigens; D001973:Bromodeoxyuridine; D002047:Buprenorphine; D003857:Deoxyuridine; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4