(PMID:20363261) In a mouse model of Down's syndrome, memantine improved spatial and recognition-memory performance. This model was characterized by partial trisomy of murine chromosome 16 exhibiting hippocampus-dependent memory deficits.
(PMID:20170739) A classic inducer of amnesia is scopolamine (strongly anticholinergic), and memantine reverted those changes (in chicks): "In experiment 2, 1.0 mM memantine reversed the scopolamine-induced amnesia, while other doses were ineffective."
(PMID:20100505) Memantine improves memory in day-old chicks exposed to isolation stress. "However, the results of Experiments 2 and 3 showed that, when chicks were exposed to isolation stress during the pre-training period, memory formation for saline-injected control animals was impaired and 5.0 mM memantine significantly improved memory in an inverted U-shaped dose response function."
(PMID:19902058) A hypothesized mechanism for improvement in mice exposed to active avoidance, and the role of latent inhibition. Habit acquisition is impaired in active-avoidant mice (Wistar rats), a single dose of memantine accelerated acquisition of the criterion. The main hypothesis being that: "[...] the preparation [memantine] can produce positive effects on memory in Alzheimer-type dementia due to primary recovery of inhibitory aspect of attention."
(PMID:1790459) Complete blockade of NMDA receptors has been shown to impair neuronal plasticity (and thus learning). Both hypo- and hyperactive glutamergic systems leads to a dysfunctional state. Due to memantine's moderate uncompetitive voltage-dependent NMDA receptor antagonism, it is postulated that it will only affect either hypo- or hyperactive glutamergic systems, but not impinge on normal NMDA function. The authors postulate that this is the mechanism by which memantine improves memory, reverses learning deficits, and is neuroprotective.
(PMID: 17445991) Aging Wistar rats were administered 20mg/kg of memantine for 21 consecutive days, and were tested in novel object recognition task (7 days after administration, ie. post-adaptation), and memantine-treated mice had unaltered recognition memory performance, whereas the mice on saline showed long-term memory deficits. The authors postulate that memantine disrupts oxidative damage to several proteins in the frontal cortex and hippocampus; both crucial regions in memory-formation and recollection. The result suggest that memantine is able to reverse age-dependent memory-deficits.
(PMID: 16611808) Acutely memantine impairs memory retention in rats. Limited study due to window of administration (24-hour window), and does not account for adaptation-period, and hypothesizes that it is untenable that memantine can be used in AD with positive results; which is obviously not what the literature suggest.
(PMID: 8963448) Female adult rats treated with memantine (30mg/kg) daily for 8 weeks showed increased long-term potentiation post-synaptic signals hippocampal synapses. In the spatial version of the Morris water-maze, both groups (memantine and saline) performed equally well, but the female mice subjected to memantine showed more selective search patterns (improved intelligence...?). The authors hypothesize that the improvement observed in patients with AD is partially due to memantine's ability to induce LTP-dependent spikes in hippocampal synapses and thus an effect on synaptic plasticity.
(PMID: 18582864) An interesting study. Rats treated with MDMA (Ecstasy) showed impaired learning in Morris water maze, but if pre-treated with memantine, this memory impairment was prevented. Moreover, memantine administration alone improved the learning of the learning task as well. The authors propose memory-deficits observed in MDMA-users could -- potentially -- be reversed or improved by memantine.
(PMID: 21479611) Pentylenetatrazol can induce human-like epilepsy symptoms in rats. This study found that memantine could ameliorate memory deficits observed in epileptic rats.
(PMID: 21440043) Memantine has antidepressant effects in a depression rat-model. The authors conclude: "In conclusion, memantine in dose of 20 mg/kg improves the sucrose consumption, reversal learning and prefrontal cortical synaptic plasticity, but impairs spatial memory, which is probably due to different extent of up-regulating NR2B receptor expression in the prefrontal cortex and hippocampus in stressed rats."
(PMID: 18378262) This study suggests that memantine both improves memory and is anxiolytic, using chronic administration of memantine at 10, 30 and 100mg/kg per day. Memantine dose-dependently affects escape latency and decreased wall swimming tendency (I expect this to be suggestive of anxiety-related behavior), increased time spent in open arms in the elevated plus-maze test, and reduced the number of isolation-induced aggressive attacks. It did not, however, in this study affect exploratory activity in the open field.
In conclusion, somewhat of a mixed bag, but we can speculate that long-term use (i.e. chronic use) of memantine either improves memory, or leaves it unaffected. Acute memantine administration clearly disrupts memory as expected, see ketamine, PCP, DXM, etc.
Unfortunately there are no actual human studies on healthy individuals and improvement of cognition. There is one pilot study showing that memantine at 20mg/day improves ADHD behavior in pediatric patients (PMID: 17343551), but warrants more study.
Moreover, as many of you may know, memantine is effective in the treatment of OCD (PMID: 19204653). It has also been shown to have mood-stabilizing effects in a rat model of mania (PMID: 21269711).
Additionally, memantine as add-on to clozapine in the treatment of schizophrenia showed improved measures of negative and positive symptoms. (PMID: 19906345
Memantine can thus be concluded to be a quite interesting molecule in many aspects, and may have potential applications in many neuropsychiatric disorders. More placebo-controlled studies are warranted.