Laboratorio di Neurofisiologia, Fondazione Santa Lucia, IRCCS, via del Fosso di Fiorano 64, 00143 Rome, Italy. Electronic address:
Published: February 2016
AI Article Synopsis
Article Abstract
Memantine is an open channel blocker that antagonizes NMDA receptors reducing the inappropriate calcium (Ca(2+)) influx occurring in presence of moderately increased glutamate levels. At the same time, memantine has the ability to preserve the transient physiological activation of NMDA receptor, essential for learning and memory formation at synaptic level. In the present study we investigated the effects exerted by memantine on striatal synaptic plasticity in rat striatal spiny projection neurons (SPNs). In vitro application of memantine in striatal slices elicited a disruption of long-term potentiation (LTP) induction and maintenance, and revealed, in the majority of the recorded neurons, a long-term depression (LTD), whose amplitude was concentration-dependent (0.3-10 μM). Interestingly, preincubation with the dopamine (DA) D2 receptor antagonist sulpiride (10 μM) prevented memantine-induced LTD and restored LTP. Moreover, the DA D2 agonist quinpirole (10 μM), similarly to memantine, induced LTD in a subgroup of SPNs. In addition, memantine-induced LTD was also prevented by the CB1 endocannabinoid receptor antagonist AM 251 (1 μM). These results suggest that the actions exerted by memantine on striatal synaptic plasticity, and in particular the induction of LTD observed in SPNs, could be attributed to its ability to activate DA D2 receptors. By contrast, blockade of NMDA receptor is not involved in memantine-induced LTD since APV (30 μM) and MK801 (10 μM), two NMDA receptor antagonists, failed to induce this form of synaptic plasticity. Our data indicate that memantine could be used as treatment of neurological disorders in which DA D2 receptor represents a possible therapeutic target.
Ketamine is an NMDA receptor antagonist commonly used as a dissociative anesthetic and analgesic. Though it is conventionally administered via the intravenous, intramuscular, or intranasal route, use as a compounded analgesic cream is becoming increasingly common. This is a case report of a 61-year-old man who was detained by the police for erratic driving.
Morphine belongs to the class of opioids and is known for its potential to cause dependence and addiction, particularly with prolonged use. Due to the associated risks, caution must be taken when prescribing and limiting its clinical use. Overexpression of N-methyl-D-aspartate (NMDA) receptors, nitric oxide and cGMP pathway has been implicated in exacerbate the development of morphine dependence and withdrawal.
As requested by the editors of this special issue of Hippocampus on Scientific Histories of Hippocampal Research, this review provides a detailed personal perspective and historical background on the research involved in a number of findings. The review includes description of the development of the water maze and its use in providing evidence to support the role of the hippocampus in spatial memory function. The review also describes how the water maze was then used in further work to support the proposal that NMDA-dependent synaptic modification in the hippocampus mediates the encoding of new spatial memories.
Neuroimmunology Program, Fundació Clínic per la Recerca Biomèdica - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona 08036, Spain.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a disorder mediated by autoantibodies against the GluN1 subunit of NMDAR. It occurs with severe neuropsychiatric symptoms that often improve with immunotherapy. Clinical studies and animal models based on patients' antibody transfer or NMDAR immunization suggest that the autoantibodies play a major pathogenic role.
