Lazaris Anelise, Bertrand Fabrice, Lazarus Christine, Galani Rodrigue, Stemmelin Jeanne, Poirier Raphaël, Kelche Christian, Cassel Jean-Christophe
Laboratoire de Neurosciences Comportementales et Cognitives, U.M.R. 7521 Université Louis Pasteur/Centre National de la Recherche Scientifique, I.F.R. 37 de Neurosciences, 12 rue Goethe, 67000 Strasbourg, France.
Brain Res. 2003 Mar 28;967(1-2):181-90. doi: 10.1016/s0006-8993(02)04272-5.
During aging, neurotransmission systems such as the cholinergic and serotonergic ones are altered. Using rats aged 3 or 24-26 months, this study investigated whether the well-described 8-OH-DPAT-induced increase of hippocampal acetylcholine release was altered in aged rats and whether it may vary according to the magnitude of age-related cognitive deficits. Long-Evans female rats aged 24-26 months were classified as good or bad performers on the basis of their reference-memory performance in a Morris water-maze task. Subsequently, the efficiency of 5-HT(1A) receptor agonist 8-OH-DPAT (0.5 mg/kg, s.c.) in triggering hippocampal acetylcholine release was evaluated by in vivo microdialysis and high performance liquid chromatography analysis. Besides a reduced baseline release in aged rats and a correlation between the baseline release and probe-trial performance in all rats, the results demonstrated that 8-OH-DPAT produced a significant increase of hippocampal acetylcholine release (peak value) in all rats, whether aged or young. While significant in bad performers (+56%), this increase did not reach significance in good performers (+32%). The results suggest that (i) some aspects of cognitive alterations related to aging might be linked to the baseline release of acetylcholine in the hippocampus, and (ii) the cholinergic innervation of the hippocampus of aged rats responds almost normally to systemic activation of 5-HT(1A) receptors, and (iii) differential alterations of cholinergic/serotonergic interactions assessed by determination of the 8-OH-DPAT-induced release of acetylcholine in the hippocampus could not be linked with clarity to the cognitive status of aged rats.
在衰老过程中，诸如胆碱能和血清素能等神经传递系统会发生改变。本研究使用3个月或24 - 26个月大的大鼠，调查了在老年大鼠中，已被充分描述的8-OH-DPAT诱导的海马乙酰胆碱释放增加是否发生改变，以及它是否会根据与年龄相关的认知缺陷程度而变化。根据24 - 26个月大的Long-Evans雌性大鼠在莫里斯水迷宫任务中的参考记忆表现，将其分类为表现好或表现差的大鼠。随后，通过体内微透析和高效液相色谱分析，评估了5-HT(1A)受体激动剂8-OH-DPAT（0.5毫克/千克，皮下注射）触发海马乙酰胆碱释放的效率。除了老年大鼠的基线释放减少以及所有大鼠的基线释放与探针试验表现之间存在相关性外，结果表明，无论老年还是年轻大鼠，8-OH-DPAT均能使海马乙酰胆碱释放显著增加（峰值）。虽然在表现差的大鼠中增加显著（+56%），但在表现好的大鼠中这种增加未达到显著水平（+32%）。结果表明：(i) 与衰老相关的认知改变的某些方面可能与海马中乙酰胆碱的基线释放有关；(ii) 老年大鼠海马的胆碱能神经支配对5-HT(1A)受体的全身激活反应几乎正常；(iii) 通过测定8-OH-DPAT诱导的海马乙酰胆碱释放来评估的胆碱能/血清素能相互作用的差异改变，无法明确地与老年大鼠的认知状态联系起来。
