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

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

NEUROBIOLOGY OF LEARNING AND MEMORY

ACADEMIC PRESS

Lugar: SAN DIEGO, CA, USA; Año: 2007 vol. 87 p. 192 - 200

1074-7427

CF-1 male mice were trained in an inhibitory avoidance (IA) task. A single gabapentin (GBP) administration (50mg/kg, ip) immediately after training enhanced retention performance 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 signiWcant 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 signiWcant diVerent 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 signiWcant decrease in the high aYnity choline uptake in the hippocampus at the end of the retention test. The pretest administration of the direct muscarinic cholinergic agonist oxotremorine (50g/kg, ip) reversed the impairment on retention performance. This reversion was prevented by the muscarinic cholinergic antagonist scopolamine (0.5mg/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 aVected memory retrieval but not memory consolidation and that this impairment may be attributable to a reduction on central cholinergic activity.Wcant 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 signiWcant diVerent 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 signiWcant decrease in the high aYnity choline uptake in the hippocampus at the end of the retention test. The pretest administration of the direct muscarinic cholinergic agonist oxotremorine (50g/kg, ip) reversed the impairment on retention performance. This reversion was prevented by the muscarinic cholinergic antagonist scopolamine (0.5mg/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 aVected memory retrieval but not memory consolidation and that this impairment may be attributable to a reduction on central cholinergic activity.