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


CONCLUSIONS
Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information.
Prickaerts
Jos
J
Department of Psychiatry and Neuropsychology, Brain and Behavior Institute, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. jprickae@prdbe.jnj.com
Sik
Ayhan
A
van der Staay
Franz Josef
FJ
de Vente
Jan
J
Blokland
Arjan
A
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004192:Discrimination, Psychological / Q000187:drug effects; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011687:Purines; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects*; D000068677:Sildenafil Citrate; D013450:Sulfones; D014236:Trichlorfon / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D007189:Indans; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010880:Piperidines; D011687:Purines; D013450:Sulfones; D000077265:Donepezil; D000068677:Sildenafil Citrate; D014236:Trichlorfon; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat