CONICET | Buscador de Institutos y Recursos Humanos

After more than a decade, the long-term clinical treatment with the anticonvulsant-antinociceptive drug gabapentin (GBP) is still related to adverse cognitive side effects. The administration of a single dose of GBP immediately after training improves retention performance of mice in an inhibitory avoidance task, probably due to enhanced consolidation caused by disinhibition of central cholinergic pathways. On the contrary, when GBP is given twice a day during 7 days, retention performance is impaired. This effect would also involve cholinergic modulation, but inhibitory, and would be due to impairment of memory retrieval. In the present work we used a monolithic implant made of GBP-loaded poly(epsilon-caprolactone) matrices, which allowed the controlled release of the drug at doses similar to those given with the repeated twice-a-day injections, but without the fluctuations of plasma levels of the drug and allowing constant levels at least during 7 days. When implants were inserted in a subcutaneous pocket in the side of the mice, immediately after training in the inhibitory avoidance task, retention performance is improved, and when the insertion was delayed 3 h after training, performance was not affected. Hence, the facilitatory effect would be due to improvement of memory consolidation. These results could lead to a clinically relevant conclusion: maintaining stable plasma levels, GBP could be administered at a total dose similar to that given with the repeated injections, but without the impairment of memory retrieval, suggesting that some of the adverse cognitive effects observed in the clinical practice could be avoided by stabilizing plasma levels of the drug.

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