Pain Pharmacology and Neuromodulation Laboratory: Animal Models, Department of Pharmacology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 sala 202, Porto Alegre, RS, 90050-170, Brazil.
Neurochem Res. 2013 Mar;38(3):494-503. doi: 10.1007/s11064-012-0941-8. Epub 2012 Dec 9.
It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 μg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.
已知反复接触阿片类药物会损害空间学习和记忆，并且海马体在药物暴露和戒断症状后具有重要的神经调节作用。因此，本研究旨在评估新生期反复吗啡处理后短期、中期和长期海马体中 BDNF、与细胞活力相关的氧化应激标志物和 TNF-α的水平。新生雄性 Wistar 大鼠在肩胛间区接受皮下注射吗啡（吗啡组）或生理盐水（对照组），从出生后第 8 天（P8）开始，每天一次，连续 7 天，在出生后第 16 天（P16）、第 30 天（P30）和第 60 天（P60）评估海马体的神经化学参数。我们首次观察到，新生期吗啡处理可在中期和长期调节 BDNF 水平，并在长期调节超氧化物歧化酶活性。此外，还观察到 TNF-α 水平存在处理和年龄的影响，而乳酸脱氢酶水平或细胞活力没有影响。这些发现表明，新生期反复吗啡处理可导致雄性大鼠海马体的神经化学变化持续存在，并表明细胞和细胞内适应在早期阿片类药物暴露后对耐受、戒断和成瘾的重要性。
