title: Novel long-term anticonvulsant treatment with gabapentin without causing memory impairment in mice.
abstract: 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.
authors.affiliation: 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
authors.forename: Mariano G
authors.initials: MG
authors.lastname: Blake
authors.forename: Mariano M
authors.initials: MM
authors.lastname: Boccia
authors.forename: Angel M
authors.initials: AM
authors.lastname: Carcaboso
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.forename: María C
authors.initials: MC
authors.lastname: Krawczyk
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Baratti
mesh_terms: 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
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin