Novel long-term anticonvulsant treatment with gabapentin without causing memory impairment in mice.
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.
Blake
Mariano G
MG
Laboratory of Neuropharmacology of Memory Processes, Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. blakion@fmed.uba.ar
Boccia
Mariano M
MM
Carcaboso
Angel M
AM
Chiappetta
Diego A
DA
Höcht
Christian
C
Krawczyk
María C
MC
Sosnik
Alejandro
A
Baratti
Carlos M
CM
D000588:Amines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D000077206:Gabapentin; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000175:diagnosis; D051379:Mice; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin