The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in hippocampal slices

K. Rutten, J.D. Vente, A. Sik, M. van Markerink, J.H.H.J. Prickaerts, A. Blokland

Research output: Contribution to journalArticleAcademicpeer-review

74 Citations (Scopus)

Abstract

Previous studies have shown memory enhancing effects of phosphodiesterase type 5 (PDE5) inhibitors in rats. However, differences in nitric oxide (NO)-mediated cyclic GMP (cGMP) signaling in the hippocampus have been described between rats and mice. In the present study we investigated the memory enhancing effects of the PDE5 inhibitor, sildenafil on memory performance in Swiss mice using the object recognition task. Sildenafil (0.3, 1 and 3 mg/kg) was administered orally directly after the first trial. The memory for the objects was retested 24 It later when mice show no memory for the familiar object. Sildenafil improved the object discrimination performance of Swiss mice at a dose of I mg/kg. Hippocampal slices of Swiss mice incubated with sildenafil (10 mu M) increased cGMP levels in varicosities in the CA3 region of the hippocampus and a number of short, thin fibers. Addition of DEA/NO, an NO donor (10 mu M), in the presence of sildenafil (10 mu M) strongly increased cGMP immunoreactivity of varicosities in the CA3 region. Double immunostaining of cGMP with the presynaptic marker synaptophysin did not reveal any co-localization of these markers under any circumstance. Taken together, inhibition of PDE5 improves object recognition memory in mice. Furthermore, a postsynaptic role of cGMP could be involved in this respect.
Original languageEnglish
Pages (from-to)11-6
JournalBehavioural Brain Research
Volume164
Issue number1
DOIs
Publication statusPublished - 1 Jan 2005

Cite this

@article{ae596bfaff8542e294065c99dd921174,
title = "The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in hippocampal slices",
abstract = "Previous studies have shown memory enhancing effects of phosphodiesterase type 5 (PDE5) inhibitors in rats. However, differences in nitric oxide (NO)-mediated cyclic GMP (cGMP) signaling in the hippocampus have been described between rats and mice. In the present study we investigated the memory enhancing effects of the PDE5 inhibitor, sildenafil on memory performance in Swiss mice using the object recognition task. Sildenafil (0.3, 1 and 3 mg/kg) was administered orally directly after the first trial. The memory for the objects was retested 24 It later when mice show no memory for the familiar object. Sildenafil improved the object discrimination performance of Swiss mice at a dose of I mg/kg. Hippocampal slices of Swiss mice incubated with sildenafil (10 mu M) increased cGMP levels in varicosities in the CA3 region of the hippocampus and a number of short, thin fibers. Addition of DEA/NO, an NO donor (10 mu M), in the presence of sildenafil (10 mu M) strongly increased cGMP immunoreactivity of varicosities in the CA3 region. Double immunostaining of cGMP with the presynaptic marker synaptophysin did not reveal any co-localization of these markers under any circumstance. Taken together, inhibition of PDE5 improves object recognition memory in mice. Furthermore, a postsynaptic role of cGMP could be involved in this respect.",
author = "K. Rutten and J.D. Vente and A. Sik and {van Markerink}, M. and J.H.H.J. Prickaerts and A. Blokland",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.bbr.2005.04.021",
language = "English",
volume = "164",
pages = "11--6",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier Science",
number = "1",

}

The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in hippocampal slices. / Rutten, K.; Vente, J.D.; Sik, A.; van Markerink, M.; Prickaerts, J.H.H.J.; Blokland, A.

In: Behavioural Brain Research, Vol. 164, No. 1, 01.01.2005, p. 11-6.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in hippocampal slices

AU - Rutten, K.

AU - Vente, J.D.

AU - Sik, A.

AU - van Markerink, M.

AU - Prickaerts, J.H.H.J.

AU - Blokland, A.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Previous studies have shown memory enhancing effects of phosphodiesterase type 5 (PDE5) inhibitors in rats. However, differences in nitric oxide (NO)-mediated cyclic GMP (cGMP) signaling in the hippocampus have been described between rats and mice. In the present study we investigated the memory enhancing effects of the PDE5 inhibitor, sildenafil on memory performance in Swiss mice using the object recognition task. Sildenafil (0.3, 1 and 3 mg/kg) was administered orally directly after the first trial. The memory for the objects was retested 24 It later when mice show no memory for the familiar object. Sildenafil improved the object discrimination performance of Swiss mice at a dose of I mg/kg. Hippocampal slices of Swiss mice incubated with sildenafil (10 mu M) increased cGMP levels in varicosities in the CA3 region of the hippocampus and a number of short, thin fibers. Addition of DEA/NO, an NO donor (10 mu M), in the presence of sildenafil (10 mu M) strongly increased cGMP immunoreactivity of varicosities in the CA3 region. Double immunostaining of cGMP with the presynaptic marker synaptophysin did not reveal any co-localization of these markers under any circumstance. Taken together, inhibition of PDE5 improves object recognition memory in mice. Furthermore, a postsynaptic role of cGMP could be involved in this respect.

AB - Previous studies have shown memory enhancing effects of phosphodiesterase type 5 (PDE5) inhibitors in rats. However, differences in nitric oxide (NO)-mediated cyclic GMP (cGMP) signaling in the hippocampus have been described between rats and mice. In the present study we investigated the memory enhancing effects of the PDE5 inhibitor, sildenafil on memory performance in Swiss mice using the object recognition task. Sildenafil (0.3, 1 and 3 mg/kg) was administered orally directly after the first trial. The memory for the objects was retested 24 It later when mice show no memory for the familiar object. Sildenafil improved the object discrimination performance of Swiss mice at a dose of I mg/kg. Hippocampal slices of Swiss mice incubated with sildenafil (10 mu M) increased cGMP levels in varicosities in the CA3 region of the hippocampus and a number of short, thin fibers. Addition of DEA/NO, an NO donor (10 mu M), in the presence of sildenafil (10 mu M) strongly increased cGMP immunoreactivity of varicosities in the CA3 region. Double immunostaining of cGMP with the presynaptic marker synaptophysin did not reveal any co-localization of these markers under any circumstance. Taken together, inhibition of PDE5 improves object recognition memory in mice. Furthermore, a postsynaptic role of cGMP could be involved in this respect.

U2 - 10.1016/j.bbr.2005.04.021

DO - 10.1016/j.bbr.2005.04.021

M3 - Article

VL - 164

SP - 11

EP - 16

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

IS - 1

ER -