Laboratory of Neuropharmacology of Memory Processes, Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Epilepsy Behav. 2010 Feb;17(2):157-64. doi: 10.1016/j.yebeh.2009.12.005. Epub 2010 Jan 15.
We previously reported that administration of a single dose of gabapentin (GBP) immediately after training improves memory of mice in an inhibitory avoidance task (IA), whereas GBP administered repeatedly for 7 days impairs memory. This is in accordance with the observation that long-term clinical treatment with GBP may be associated with adverse cognitive side effects. In the present work we used a GBP-loaded poly(epsilon-caprolactone) implant, allowing controlled release of the drug and maintenance of constant plasma levels over 1 week. When GBP-loaded implants were inserted subcutaneously into mice, immediately after training in the IA task, memory consolidation was enhanced. Moreover, GBP released from implants had an anticonvulsant action against pentylenetetrazole-induced seizures. These results suggest that maintenance of stable GBP plasma levels could protect against seizures without causing memory impairment. Hence, the adverse cognitive effects might be avoided by stabilizing plasma levels of the drug.
我们之前报道过，在训练后立即给予单剂量加巴喷丁（GBP）可改善小鼠在抑制性回避任务（IA）中的记忆，而连续 7 天给予 GBP 则会损害记忆。这与长期临床使用 GBP 可能与认知副作用相关的观察结果一致。在本工作中，我们使用了负载 GBP 的聚（ε-己内酯）植入物，允许药物的控释和在 1 周内维持恒定的血浆水平。当 GBP 负载的植入物在 IA 任务训练后立即皮下插入小鼠时，记忆巩固得到增强。此外，从植入物中释放的 GBP 对戊四氮诱发的癫痫发作具有抗惊厥作用。这些结果表明，维持稳定的 GBP 血浆水平可以预防癫痫发作而不会导致记忆损伤。因此，通过稳定药物的血浆水平可以避免认知不良影响。
