Acute treatment with low doses of memantine does not impair aversive, non-associative and recognition memory in rats.
Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist, which has been employed in the clinic as a neuroprotective agent for the treatment of several dementias, particularly Alzheimer's disease. In this study, we evaluated pharmacological effects of the acute administration of memantine on memory process. Memory retention scores were evaluated in normal adult Wistar rats injected with saline and memantine (2, 5, 10, and 20 mg/kg, IP) and then subjected to the step-down inhibitory avoidance task, habitation to an open-field apparatus, and object recognition task. The treatment with higher doses of memantine (10 and 20 mg/kg) injected 60 min before or immediately after training-session impaired acquisition and retention of aversive memory in the inhibitory avoidance task. In addition, higher doses of memantine injected 60 min before the first open-field exposure also impaired habituation during the second exposure to the apparatus. No significant differences were observed in the performance of rats treated with memantine, in all doses tested, compared to saline-treated rats in the object recognition task. Notably, we observed that at 5 mg/kg, memantine increased spontaneous locomotion and exploration in the rat open-field test. In conclusion, present findings support the view that memantine at lower doses did not affect memory formation in normal rats, but at high doses memantine, induce hyperlocomotion, which could bias the interpretation of the animal behavior assessed in memory tests.
Réus
Gislaine Z
GZ
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciuma, SC, Brazil.
Valvassori
Samira S
SS
Machado
Roberta A
RA
Martins
Márcio R
MR
Gavioli
Elaine C
EC
Quevedo
João
J
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine