Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

Abstract

Rationale: Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes.Objective: We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. Methods: The object recognition task measures whether rats remembered an object they have explored in a previous learning trial. All drugs were given orally 30 min before or immediately after learning to study acquisition and consolidation, respectively. Results: Sildenafil given immediately after the first trial improved the memory performance after 24 h and resulted in an inverted U-shaped dose-effect curve with the peak dose at 3 mg/kg. When given before the first trial, sildenafil also improved the memory performance. However, the dose needed for the best performance under this condition was 10 mg/kg, suggesting that the dose-effect curve shifted to the right. This can be explained by the metabolic clearance of the high dose of sildenafil. Donepezil had no memory improving effect when given after the first trial. However, when given before the first trial, a gradually increasing dose-effect curve was found which had its maximum effect at the highest dose tested (1 mg/kg). Likewise, only when metrifonate (30 mg/kg) was given before the first trial did rats show an improved memory performance. Conclusion: Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information.

The Novel α7 Nicotinic Acetylcholine Receptor AgonistN-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[2-(methoxy)phenyl]-1-benzofuran-2-carboxamide Improves Working and Recognition Memory in Rodents

“…This reduces the effects of the individual preference of mice for particular locations or particular objects. The object recognition test provides measures for exploration and discrimination, i.e., noncognitive effects of a drug can be distinguished from effects on memory performance (for details, see Prickaerts et al, 2005). The times spent exploring the familiar and new object during T2 were represented as a and b, respectively.…”

Object recognition testing: Methodological considerations on exploration and discrimination measures

“…Before testing starts, the animals are often familiarized or habituated and protocols differ greatly between laboratories. In some laboratories the animals are allowed to familiarize with only the apparatus [2,11,12,23], others also introduce objects in the pre-experimental phase [25] or even let the animals undergo the full testing procedure, including injections [34,35]. Even more fundamental, there is no consensus about the definition of object investigation.…”

“…Both drugs have proven reliably to attenuate the novel object preference in a 1 h retention delay, likely due to drug induced memory impairment [6,39,40]. 24 h retention intervals were used to investigate drug effects on natural forgetting, as our male Wistar rats normally do not discriminate anymore between the novel and the familiar object after such an interval [1,8,[33][34][35].…”

Effects of cholinesterase inhibitor metrifonate on naive rats and rats with a model of hypoxia-induced impaired memory

“…Jos Prickaerts et al [12] observed in healthy adult rats the memory-enhancing effects of metrifonate in the object recognition task, and concluded that metrifonate (30 mg/kg) given before the first trial showed an improved memory performance in rats. According to their findings, the administration of a drug before the learning trial should have an effect on the acquisition of information.…”