Effects of the Nitric Oxide Synthase Inhibitor L-NAME on Recognition and Spatial Memory Deficits Produced by Different NMDA Receptor Antagonists in the Rat

Abstract

There is consistent experimental evidence that noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, such as ketamine, MK-801, and phencyclidine (PCP), impair cognition and produce psychotomimetic effects in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain. The implication of NO in learning and memory is well documented. This study was designed to investigate the ability of the NO synthase inhibitor L-NAME to antagonize recognition and spatial memory deficits produced by the NMDA receptor antagonists, MK-801 and ketamine, in the rat. L-NAME (1-3 mg/kg) counteracted MK-801-(0.1 mg/kg) and ketamine (3 mg/kg)-induced performance impairments in the novel object recognition task. L-NAME (10 mg/kg) attenuated ketamine (15 mg/kg)-induced spatial working memory and retention deficits in the radial water maze paradigm. L-NAME, applied at 3 mg/kg, however, disrupted rodents' performance in this spatial memory task. The present findings indicate (1) that L-NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and (2) that L-NAME alone differentially affects rodents' spatial memory.

Anesthetic Ketamine Impairs Rats' Recall of Previous Information

“…A single posttraining injection of 1 and 3 mg/kg L-NAME antagonized the ketamine-induced performance deficits in this recognition memory paradigm. In agreement with previous reports, 14,16 L-NAME at a dose of 10 mg/kg was ineffective at counteracting recognition memory impairments caused by ketamine. Because this lack of effect was observed after short-term treatment, it is not attributable to tolerance.…”

“…23 The current findings on subanesthetic ketamine are apparently in contrast to previous research, in which the same dose (3 mg/kg) of it impaired rats' recognition memory. 14 The experimental design of that study 14 was consistently different from that used in the current experimentation. In the previously mentioned study, 14 treatment and experimentation were performed only under standard environmental conditions (21°C).…”

“…14 The experimental design of that study 14 was consistently different from that used in the current experimentation. In the previously mentioned study, 14 treatment and experimentation were performed only under standard environmental conditions (21°C). Drug administration under the warm condition (25°C) was never performed.…”

“…Finally, L-NAME was able to reverse recognition and spatial memory deficits produced by subanesthetic doses (3 mg/kg) of ketamine in rats. 14 After taking the described evidence into consideration, the first aim of our study was to evaluate the effects of posttraining administration of anesthetic ketamine on rats' recognition memory and to determine whether these effects were related to the hypothermic properties of ketamine. Subsequently, the efficacy of L-NAME (1, 3, and 10 mg/kg intraperitoneally) to counteract the expected recognition memory deficits induced by anesthetic ketamine was also assessed.…”

Διερεύνηση της δράσης των παραγώγων του Crocus sativus L. επί του κεντρικού νευρικού συστήματος στον επίμυ

“…Όλες οι ενέσεις έγιναν αμέσως μετά την Τ1, έτσι ώστε 60 λεπτά μετά, κατά την Τ2 να έχουν ήδη παρέλθει πιθανές παρενέργειες από τη χορήγηση της κεταμίνης (υπερκινητικότητα, στερεοτυπίες, αταξία). Η δόση της κεταμίνης που επιλέχθηκε για την πρόκληση μνημονικών ελλειμμάτων ήταν αυτή των 3 mg/kg διότι βρέθηκε αποτελεσματική σε προγενέστερη μελέτη (Boultadakis & Pitsikas, 2010 Ο παρατηρητής αποχωρεί από το δωμάτιο, ώστε η παρουσία του να μην επηρεάζει τη συμπεριφορά του πειραματόζωου. Έπειτα γίνεται η επεξεργασία των δεδομένων κατά την οποία ελέγχουμε δύο παραμέτρους: το χρόνο που το ζεύγος των επίμυων αφιέρωσε σε κοινωνική αλληλεπίδραση και την κινητικότητα ως δείκτη γενικής δραστηριότητας.…”