Effects of the uncompetitive nmda receptor antagonist memantine on recognition memory in rats.
Memantine is an NMDA receptor antagonist that has been recently approved in EU for the treatment of moderate to severe Alzheimer's disease. The previous studies have not allowed for the evaluation of the possible effects of this drug at therapeutic doses on different forms of memory. To address this question, we administered memantine to adult rats, using doses 2.5 or 5 mg/kg and evaluated the effects of these doses on open field activity and recognition memory. Memantine or saline was administered daily by intraperitoneal injection beginning on the day of behavioral testing and continuing 5 days. The main results of experiments are as follows: the memantine treatment produced a dose-related suppression of total ambulations. There was no significant impairment in detecting spatial and object novelty in the 2.5 mg/kg memantine treated rats. However, the 5 mg/kg intraperitoneal dose of memantine disrupted both recognition memory and locomotor behaviors. Our evaluation of memantine reveals that at doses lower than are required for neuroprotection disrupt memory. This raises the possibility that the beneficial effects seen in AD patients may be attributable to the interaction of memantine with other transmitter systems.
Dashniani
M
M
I. Beritashvili Institute of Physiology, Tbilisi, Georgia.
Burjanadze
M
M
Beselia
G
G
Chkhikvishvili
N
N
Naneishvili
T
T
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000009:adverse effects*; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D021641:Recognition, Psychology / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine