The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents

F.J. van der Staay; K. Rutten; L. Barfacker; J. Devry; C. Erb; H. Heckroth; D. Karthaus; A. Tersteegen; M. van Kampen; A. Blokland; J.H.H.J. Prickaerts; K.G. Reymann; U.H. Schroder; M. Hendrix

doi:10.1016/j.neuropharm.2008.07.005

The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents

F.J. van der Staay^*, K. Rutten, L. Barfacker, J. Devry, C. Erb, H. Heckroth, D. Karthaus, A. Tersteegen, M. van Kampen, A. Blokland, J.H.H.J. Prickaerts, K.G. Reymann, U.H. Schroder, M. Hendrix

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 mu M, but not 30 mu M BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31 - to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease.

Original language	English
Pages (from-to)	908-918
Journal	Neuropharmacology
Volume	55
Issue number	5
DOIs	https://doi.org/10.1016/j.neuropharm.2008.07.005
Publication status	Published - 1 Jan 2008

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10.1016/j.neuropharm.2008.07.005

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van der Staay, F. J., Rutten, K., Barfacker, L., Devry, J., Erb, C., Heckroth, H., Karthaus, D., Tersteegen, A., van Kampen, M., Blokland, A., Prickaerts, J. H. H. J., Reymann, K. G., Schroder, U. H., & Hendrix, M. (2008). The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents. Neuropharmacology, 55(5), 908-918. https://doi.org/10.1016/j.neuropharm.2008.07.005

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title = "The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents",

abstract = "The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 mu M, but not 30 mu M BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31 - to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease. ",

author = "{van der Staay}, F.J. and K. Rutten and L. Barfacker and J. Devry and C. Erb and H. Heckroth and D. Karthaus and A. Tersteegen and {van Kampen}, M. and A. Blokland and J.H.H.J. Prickaerts and K.G. Reymann and U.H. Schroder and M. Hendrix",

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van der Staay, FJ, Rutten, K, Barfacker, L, Devry, J, Erb, C, Heckroth, H, Karthaus, D, Tersteegen, A, van Kampen, M, Blokland, A, Prickaerts, JHHJ, Reymann, KG, Schroder, UH & Hendrix, M 2008, 'The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents', Neuropharmacology, vol. 55, no. 5, pp. 908-918. https://doi.org/10.1016/j.neuropharm.2008.07.005

TY - JOUR

T1 - The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents

AU - van der Staay, F.J.

AU - Rutten, K.

AU - Barfacker, L.

AU - Devry, J.

AU - Erb, C.

AU - Heckroth, H.

AU - Karthaus, D.

AU - Tersteegen, A.

AU - van Kampen, M.

AU - Blokland, A.

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

AU - Reymann, K.G.

AU - Schroder, U.H.

AU - Hendrix, M.

PY - 2008/1/1

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N2 - The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 mu M, but not 30 mu M BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31 - to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease.

AB - The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 mu M, but not 30 mu M BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31 - to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease.

U2 - 10.1016/j.neuropharm.2008.07.005

DO - 10.1016/j.neuropharm.2008.07.005

M3 - Article

SN - 0028-3908

VL - 55

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JO - Neuropharmacology

JF - Neuropharmacology

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ER -