Influence of N-methyl D-aspartate receptor mechanism on WIN55,212-2-induced amnesia in rat dorsal hippocampus

Abstract

In this study, we investigated the effects of both N-methyl D-aspartate (NMDA) and MK-801 on WIN55,212-2(WIN)-induced amnesia in rats. Step-through inhibitory avoidance of memory was used to examine the retrieval of memory, 24 h after training. All drugs were injected bilaterally into the dorsal hippocampus (intra-CA1) of rats. Pretraining and posttraining or pretesting administration of the nonselective CB1/CB2 receptor agonist, WIN (0.5 µg/rat), decreased the step-through latency. However, amnesia induced by pretraining or posttraining injections of WIN was reversed by a pretest administration of WIN (0.25 and 0.5 µg/rat). Pretest microinjections of different doses of NMDA (0.1, 0.5, and 1 µg/rat) elicited no response, but NMDA (0.5 and 1 µg/rat) did induce full recovery from amnesia induced by WIN (0.5 µg/rat). The posttraining and pretest injection of a higher dose of the NMDA receptor antagonist, MK801 (MK; 4 µg/rat), caused an impairment in the memory retrieval. However, amnesia induced by posttraining injections of MK (4 µg/rat) was reversed by a pretest administration of MK (4 µg/rat). In addition, pretest administration of different doses of the antagonist (2 and 4 µg/rat) induced full recovery of WIN-induced amnesia, but did not influence memory recovery in the subjects, which had received posttraining (0.5 µg/rat) and pretest WIN (0.25 and 0.5 µg/rat). Pretesting coadministration of ineffective doses of WIN (0.1 µg/rat) with NMDA (0.1 µg/rat), but not with MK (1 µg/rat), restored WIN-induced (0.5 µg/rat) amnesia. It can be concluded that the NMDA receptor mechanism located in the dorsal hippocampus may be involved in WIN-induced amnesia.

The effects of CA1 5HT4 receptors in MK801-induced amnesia and hyperlocomotion

“…Systemic or intra-cerebral administration of MK801 has been shown to affect formation of memory [8]. It has been revealed that NMDA receptor antagonists impaired memory via reduction in nitric oxide level and subsequent cGMP production in the brain [17]. In agreement with our result, both competitive and noncompetitive NMDA receptor antagonists have been reported to impair memory in various behavioral tests [8,17].…”

“…It has been revealed that NMDA receptor antagonists impaired memory via reduction in nitric oxide level and subsequent cGMP production in the brain [17]. In agreement with our result, both competitive and noncompetitive NMDA receptor antagonists have been reported to impair memory in various behavioral tests [8,17]. Furthermore, although most investigations show memory-impairing effects of NMDA receptor antagonists, there is evidence that at least under some experimental conditions, MK801 can display memory-enhancing properties [4,14].…”

“…Furthermore, although most investigations show memory-impairing effects of NMDA receptor antagonists, there is evidence that at least under some experimental conditions, MK801 can display memory-enhancing properties [4,14]. It seems that the effects of NMDA receptor blockade by MK-801 on memory depend on factors such as familiarity with training environment [8] and time of administration [17]. Also, our results indicated that there was a significant increase of locomotor activity in response to MK801 compared to the control group.…”

Activation of cannabinoid CB1 receptors in the ventral hippocampus improved stress-induced amnesia in rat

“…CB 1 receptors, the most abundant G-protein-coupled receptors in the central nervous system, are densely expressed in the hippocampus (Svízenská et al, 2008). Up to now, previous studies have reported that the activation or inactivation of Cannabinoid CB1 receptors modulates memory processing (Jamali-Raeufy et al, 2011;Takahashi et al, 2005). Basavarajappa and Subbanna (2014) also reported that Cannabinoid CB1 receptors agonist injection impaired spatial information processing and object recognition memory.…”

Original article Involvement of D 2 /D 2 dopamine antagonists upon open-arms exploratory behaviours induced by intra-nucleus accumbens shell administration of N-methyl-D-aspartate

“…On the other hand, glutamate is known as one of the most excitatory neurotransmitters modulating learning, memory and anxiety-like behaviours in different parts of the brain [33,94]. With respect to the preferential agonists, at least three subtypes have been identified for glutamate, including N-methyl-D-aspartate (NMDA), AMPA and kainate [57].…”