Opposite effects of a single versus repeated doses of gabapentin on retention performance of an inhibitory avoidance response in mice.
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 significant impairment on retention performance 12h 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 microg/kg, ip) reversed the impairment on 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.
Blake
Mariano G
MG
Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. blakion@fmed.uba.ar
Boccia
Mariano M
MM
Acosta
Gabriela B
GB
Höcht
Christian
C
Baratti
Carlos M
CM
D000588:Amines / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002794:Choline / Q000493:pharmacokinetics; D003214:Conditioning, Classical / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004597:Electroshock / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000097:blood; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D014316:Tritium / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000097:blood
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D000077206:Gabapentin; D002794:Choline