nitroarginine and Amnesia

N-methyl-D-aspartate (NMDA) receptor and nitricoxide syntheses are the emerging target sites for development of novel drug molecules because their modulation affects the long term potentiation (LTP) process. NMDA receptor antagonists and nitric oxide synthase inhibitors induce amnesia in animals and therefore have been employed for evaluation of efficacy of several novel antiamnesic agents.Bacopa monniera Linn (syn. Brahmi) is commonly used in the ancient Indian medical system for improvement of memory deficit.We have earlier described the involvement of GABAergic and cholinergic system to account for the antiamnesic effects of B. monniera on diazepam- and scopolamine-induced amnesia.In extension to our previous study this study was designed to investigate the downstream mechanism of B. monniera by evaluation of its effect on MK-801 (an NMDA receptor antagonist) and N(w)-nitro-L-arginine (L-NNA) (a nitric oxide inhibitor)induced memory deficit. We used a Morris water maze scale and compared the degree of reversal of amnesia induced by the two agents. Male Swiss albino mice were subjected to a Rotarod muscle incoordination test followed by water maze tasks.Our data revealed that L-NNA and MK-801 produced anterograde and retrograde amnesia and B. monniera significantly attenuated the L-NNA-induced anterograde amnesia, partially reversing L-NNA-induced retrograde amnesia. On the other hand, B. monniera neither attenuated the MK-801-induced anterograde amnesia nor improved retrograde amnesia caused by it.

Topics: Amnesia; Amnesia, Anterograde; Amnesia, Retrograde; Analysis of Variance; Animals; Bacopa; Dizocilpine Maleate; Excipients; Male; Maze Learning; Memory; Mice; Motor Activity; Nitroarginine; Phytotherapy; Plant Preparations; Polysorbates

Investigations indicate that the induction of long-term potentiation (LTP) may be mediated by postsynaptic N-methyl-D-aspartate (NMDA) receptors and that the maintenance of LTP may be initiated by nitric oxide (NO), a retrograde messenger carrying signals backward from the postsynaptic to the presynaptic neuron. The present study compared amnestic effects of dizocilpine maleate (MK-801), an NMDA receptor antagonist, and nitro-L-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine (L-NOARG), nitric oxide (NO) inhibitors, in goldfish, using active-avoidance conditioning as the learning paradigm. The results showed that MK-801 and NO inhibitors produced anterograde amnesia at doses that did not impair performance processes necessary for learning to occur. Furthermore, MK-801 did not produce retrograde amnesia, whereas L-NAME did, suggesting that MK-801 impaired learning whereas NO inhibitors impaired memory consolidation and possibly also learning.

Topics: Amnesia; Analysis of Variance; Animals; Avoidance Learning; Dizocilpine Maleate; Electroshock; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Goldfish; Long-Term Potentiation; Memory; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroarginine; Receptors, N-Methyl-D-Aspartate; Time Factors

It has been hypothesized that nitric oxide (NO) may act as a 'retrograde messenger' in the CNS, mediating intersynaptic communication in the context of neural plasticity during memory formation. To test this hypothesis the effects of the competitive NO synthase inhibitor N-nitro-L-arginine (NARG) on memory retention has been studied in a one-trial passive avoidance task in the day-old chick. Intracerebral injections before training into the intermediate medial hyperstriatum ventrale (IMHV), an area that is of crucial importance in learning in the chick, produced amnesia in this task when tested at various time points from 30 min to 24 h after training. Time- and dose dependencies of NARG when injected i.p. or i.c. were evaluated. Injection into one IMHV alone (left or right) proved to be sufficient to produce amnesia. Diffusion of NARG into the untreated hemisphere was ruled out by injecting it with L-arginine, which competes with NARG and prevents inhibition of NO synthase. Additional tests showed that the amnestic effect is not due to state-dependent learning, nor to interference of the drug with general motor ability or motivation.

Topics: Amnesia; Animals; Arginine; Avoidance Learning; Cerebral Ventricles; Chickens; Corpus Striatum; Dose-Response Relationship, Drug; Female; Injections, Intraventricular; Male; Memory; Neuronal Plasticity; Nitric Oxide; Nitroarginine; Signal Transduction; Time Factors

Memory formation is presumed to require retrograde communication across synaptic junctions. Nitric oxide (NO) is a putative retrograde messenger at N-methyl-D-aspartate (NMDA)-mediated synapses [8, 9]. Inhibitors of nitric oxide synthesis block initiation of long-term potentiation [2, 3, 19]. Memory for a one-trial passive avoidance task in the young chick involves an NMDA-linked intracellular cascade culminating in lasting modulation of synaptic morphology and [6, 18]. Here we show that injection of the nitric oxide synthase inhibitor N-nitro-L-arginine prior to training results in amnesia for the passive avoidance task; the amnesia can be overcome by injecting L-arginine along with the inhibitor. Thus we have verified for the first time experimentally that NO plays a role in memory formation.

Topics: Amino Acid Oxidoreductases; Amnesia; Animals; Arginine; Avoidance Learning; Chickens; Memory; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine