Memantine prevents memory consolidation failure induced by soluble beta amyloid in rats.

It has been well documented that beta-amyloid (A beta) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sA beta) are involved in AI-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sA beta, acutely injected intracerebrally (i.c.v., 4 mu M), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of A beta on synaptic plasticity and memory. Thus, we also investigated the effects of sA beta on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sA beta administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sA beta 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sA beta was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sA beta peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sA beta-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment.