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 -hs 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.

阿片类药物（包括吗啡）是强有力的镇痛药，具有很高的滥用潜力。在啮齿动物中，长期的鸦片暴露或自我给药会对海马依赖性功能产生负面影响，这种影响可能部分归因于充分证明的鸦片诱导的齿状回（DG）前体增殖和神经发生抑制作用。然而，最近有报道称静脉内（iv）吗啡自我给药（MSA）可以增强新大鼠DG神经元的存活率。为了调和这些不同的结果，我们使用大鼠iv MSA评估1）更高剂量的MSA范型是否还会增加新的DG神经元存活率；2）MSA如何影响DG神经发生不同阶段的细胞，尤其是成熟和存活；和3）是否在禁欲期间持续存在MSA诱导的DG神经发生变化。为了标记基础增殖水平，大鼠在静脉内MSA或生理盐水自我给药（SSA）的21天（D）之前的24小时内接受了S期标记溴脱氧尿苷（BrdU，ip）。在SA（0-D）后立即或在笼中4周（退出28-D）后，使用立体学方法定量DG增殖前体（或细胞周期中的细胞； Ki67 +细胞），成神经细胞/未成熟神经元（DCX +细胞）和存活的DG颗粒细胞（BrdU +细胞）。分析显示，MSA和SSA大鼠在0-D或28-D时间点对这些神经发生相关标记具有免疫阳性的DG细胞数量相似。这些负面数据突出了实验参数，时间点选择和量化方法对神经发生结果的影响，并在大量文献中讨论了鸦片剂对DG神经发生的负面影响。