Contrasting effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 on performance of an operant delayed matching to position task in rats

Abstract

The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly "forgetting" curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a marked delay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a marked delay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS)

Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5

“…The earliest interval at which memory is affected remains unclear. Tonkiss et al (1988) found that a memory delay of 18 sec was sufficient to see a deficit in AP5 treated animals in an operant drl task; Cole et al (1993) found a deficit at 5, 15, and 30 sec in her study in which memory delay was systematically varied, while Li et al (1997), using a delay-interposed radial maze task and CGS19755, found that a 5-min delay was sufficient to see a deficit. The exact time scale of memory formation may vary across tasks or even as a function of the speed with which animals complete a task.…”

“…Tonkiss and Rawlins (1991) found that AP5-treated rats were impaired on a one-trial T-maze alternation task at long ITIs, but unimpaired at shorter ones. Using an operant analogue of the present DMP task, Cole et al (1993) found that i.p. injections of CPP (but not MK801) caused a delay-dependent deficit in performance, but a ceiling effect at zero delay complicates interpretation of this study.…”

The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats

“…The delayed non-matching to position task is considered to be a useful tool for assessing working memory in a spatial context and the water maze task for assessing acquisition of spatial representational memory. Both of these memory processes are reported to be critically dependent on the normal function of hippocampal circuits which utilize excitatory amino acids as neurotransmitters (Morris et al, 1986;Morris, 1989;Aggleton et al, 1992;Ohno et al, 1992;Cole et al, 1993). Furthermore, both of these memory processes can become impaired in various forms of cholinergic hypofunction (Dunnett, 1988;Gallagher and Pelleymounter, 1988).…”

New life in an old idea: The synaptic plasticity and memory hypothesis revisited

“…If a treatment, such as an NMDA receptor antagonist administered during encoding, has minimal effects on retrieval tested at a short delay, but a much larger effect at a long delay, it is difficult to see how an explanation couched solely in terms of sensorimotor side effects can be valid. The application of competitive NMDA receptor antagonists has been found to cause a delay-dependent deficit in a variety of different behavioral paradigms, including operant DRL (Tonkiss et al, 1988), T-maze alternation (Tonkiss and Rawlins, 1991), operant delayed matching-to-position (Cole et al, 1993), contextual fear conditioning (Fanselow et al, 1994), and a delay-interposed radial maze task (Li et al, 1997). All these studies used intracerebroventricular or systemic drug delivery, the effects of which will not have been limited to the hippocampal formation.…”