Opposite effects of a single versus repeated doses of gabapentin on retention performance of an inhibitory avoidance response in mice

MG BLAKE; MM BOCCIA; GB ACOSTA; C HOCHT; CM BARATTI

Neurobiol Learn Mem.

Academic Press

Lugar: United States; Año: 2007 vol. 87 p. 192 - 200

CF-1 male mice were trained in an inhibitory avoidance (IA) task. A single gabapentin (GBP) administration (50 mg/kg, ip) immediately after training retention when mice were tested 8 days after training. On the contrary, when the same dose of the anticonvulsant drug was given twice a day for 7 days (repeated treatment), a significant impairment on retention performance 12 h after the last injection of GBP was observed. When the retention test was delayed 7 days after the end of the repeated treatment, the retention performance was not significant different from the control group, whereas if the retention test was delayed 14 days, retention performance was higher than  control group but similar to that observed  when GBP was administered once immediately after training. The impairment on retention performance was correlated with a significant decrease in the high affinity choline uptake in the hippocampus at the end of the retention test. The pretest administration of the direct muscarinic cholinergic agonist oxotremorine (50 mg/kg, ip) reversed the impairment on the retention performance. This reversion was prevented by the muscarinic cholinergic antagonist scopolamine (0.5 mg/kg, ip). Taken together, these results suggest that the impairment on retention performance of an IA task in mice induced by repeated administration of GBP affected memory retrieval but not memory consolidation and that this impairment may be attributable to a reduction on central cholinergic activity