A within-subject cognitive battery in the rat: differential effects of NMDA receptor antagonists

Abstract

NMDA receptor-dependent mechanisms are requisite in the acquisition of a simple conditional discrimination and consolidation of extinction. Their role in working memory and reversal tasks appear to be less critical and potentially specific to the paradigm and NMDA receptor antagonist used. It is clearly misleading to generalise across NMDA antagonists with respect to their preclinical cognitive profile.

A comparison of the effects of ketamine and phencyclidine with other antagonists of the NMDA receptor in rodent assays of attention and working memory

“…Such an interpretation would be more consistent with the markedly inhibitory profile of these compounds on instrumental responding (Gilmour et al 2009) and increases in response latencies and omissions in the absence of any negative impact on accuracy in the DMTP task. However, previous work has shown that NVP-AAM077 is relatively ineffective at blocking both acquisition and extinction of a visuo-auditory discrimination, whilst memantine clearly blocks both of these effects in this task (Dix et al 2010) at doses that decrease response latencies in the present 5CSRT, consistent with findings of mnemonic deficits in otherwise normal animals by others (Creeley et al 2006). Also consistent with this are reports of deficits in recognition memory in normal humans given memantine (Rammsayer 2001).…”

“…All doses refer to the base weights of compounds. Doses and routes of administration were chosen on the basis of previously conducted studies (Gilmour et al 2009;Dix et al 2010) and a general assessment of existing published literature in this field.…”

“…However, Gilmour et al (2009) have shown that NMDAR antagonists can have substantially different effects on motor and motivational measures, as indicated by qualitative changes in instrumental responding to variable interval schedules. Furthermore, whilst NMDA receptor-dependent mechanisms are requisite in the acquisition of, for example, a simple conditional discrimination or the consolidation of extinction, their role in working memory and reversal learning tasks appears to be less critical and potentially specific to the paradigm and NMDAR antagonist used (Dix et al 2010). It is therefore clearly misleading to generalise across NMDAR antagonists with respect to their preclinical cognitive profile.…”

Differential Effects of an NR2B NAM and Ketamine on Synaptic Potentiation and Gamma Synchrony: Relevance to Rapid-Onset Antidepressant Efficacy

“…In these previous studies, CP-101,606 was effective at reducing haloperidol-induced catalepsy and neuropathic pain in rats over the dose range (2-20 mg/kg) used in the present study. Furthermore, comparative effects of ketamine and CP-101,606 over the dose ranges used in this study in a number of different behavioral paradigms have also been reported (Dix et al, 2010;Gilmour et al, 2012;Smith et al, 2011).…”

Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning

“…This is not to say that GluN2B-containing NMDA receptors do not contribute at all to certain forms of discrimination learning. Indeed, more complex discriminations that require multiple days of training to achieve asymptotic performance and have longer consolidation periods may be more sensitive to GluN2B receptor blockade (Dix et al 2010). Indeed, when learning takes place over several days, mice lacking GluN2B receptors in the forebrain show significant impairments in cortico-hippocampal-dependent tasks (von Engelhardt et al 2008;Brigman et al 2010).…”