Abstract |
Cyclic nucleotides viz cGMP and cAMP are known to play an important role in learning and memory processes. Enhancement of cyclic nucleotide signalling through inhibition of phosphodiesterases ( PDEs) has been reported to be beneficial in several neurodegenerative disorders associated with cognitive decline. The present study was undertaken to investigate the effect of RO-20-1724-a PDE4 inhibitor on streptozotocin (STZ) induced experimental sporadic dementia of Alzheimer's type. The STZ was injected twice intracerebroventrically (3 mg/kg i.c.v.) on alternate days (day 1 and day 3) in rats. The STZ injected rats were treated with RO-20-1724 (125, 250 and 500 μg/kgi.p.) for 21 days following first i.c.v. STZ administration. Learning and memory in rats were assessed by passive avoidance [PA (days 14 and 15)] and Morris water maze [MWM (days 17, 18, 19, 20 and 21)] following first i.c.v. STZ administration. On day 22 rat cerebral homogenate was used for all the biochemical estimations. The pharmacological inhibition of PDE4 by RO-20-1724 significantly attenuated STZ induced cognitive deficit and oxidative stress. RO-20-1724 was found to not only improve learning and memory in MWM and PA paradigms but also restore STZ induced elevation in cholinesterase activity. Further, RO-20-1724 significantly reduced malondialdehyde and nitrite levels, and restored the glutathione levels indicating attenuation of oxidative stress. Current data complement previous studies by providing evidence for a subset of cognition enhancing effects after PDE4 inhibition. The observed beneficial effects of RO-20-1724 in spatial memory may be due to its ability to restore cholinergic functions and possibly through its antioxidant mechanisms.
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Authors | Vivek Sharma, Ashu Bala, Rahul Deshmukh, K L Bedi, P L Sharma |
Journal | Pharmacology, biochemistry, and behavior
(Pharmacol Biochem Behav)
Vol. 101
Issue 2
Pg. 239-45
(Apr 2012)
ISSN: 1873-5177 [Electronic] United States |
PMID | 22285388
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Neuroprotective Agents
- Phosphodiesterase 4 Inhibitors
- 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
- Streptozocin
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Topics |
- 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
(administration & dosage)
- Animals
- Avoidance Learning
(drug effects)
- Cognition Disorders
(chemically induced, enzymology, prevention & control)
- Dose-Response Relationship, Drug
- Injections, Intraventricular
- Male
- Neuroprotective Agents
(administration & dosage)
- Oxidative Stress
(drug effects)
- Phosphodiesterase 4 Inhibitors
(administration & dosage)
- Random Allocation
- Rats
- Rats, Wistar
- Streptozocin
(administration & dosage, toxicity)
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