Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801

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Abstract

The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1 mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3 mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1 mg/kg (p.o.) in the scopolamine model and 0.3-3 mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1 mg/kg) and PQ-10 (0.3 mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1 mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement. (c) 2012 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalBehavioural Brain Research
Volume236
DOIs
Publication statusPublished - 1 Jan 2013

Keywords

  • Phosphodiesterase
  • cGMP
  • cAMP
  • BAY 60-7550
  • PQ-10
  • Object recognition
  • Memory
  • ACUTE TRYPTOPHAN DEPLETION
  • LONG-TERM POTENTIATION
  • RECOGNITION MEMORY
  • CYCLIC-GMP
  • PHOSPHODIESTERASE 10A
  • IMMUNOHISTOCHEMICAL LOCALIZATION
  • INDUCED IMPAIRMENTS
  • PERIRHINAL CORTEX
  • RAT HIPPOCAMPUS
  • CGMP

Cite this

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title = "Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801",
abstract = "The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1 mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3 mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1 mg/kg (p.o.) in the scopolamine model and 0.3-3 mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1 mg/kg) and PQ-10 (0.3 mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1 mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement. (c) 2012 Elsevier B.V. All rights reserved.",
keywords = "Phosphodiesterase, cGMP, cAMP, BAY 60-7550, PQ-10, Object recognition, Memory, ACUTE TRYPTOPHAN DEPLETION, LONG-TERM POTENTIATION, RECOGNITION MEMORY, CYCLIC-GMP, PHOSPHODIESTERASE 10A, IMMUNOHISTOCHEMICAL LOCALIZATION, INDUCED IMPAIRMENTS, PERIRHINAL CORTEX, RAT HIPPOCAMPUS, CGMP",
author = "O.A.H. Reneerkens and K. Rutten and E. Bollen and T. Hage and A. Blokland and H.W.M. Steinbusch and J. Prickaerts",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.bbr.2012.08.019",
language = "English",
volume = "236",
pages = "16--22",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier Science",

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Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801. / Reneerkens, O.A.H.; Rutten, K.; Bollen, E.; Hage, T.; Blokland, A.; Steinbusch, H.W.M.; Prickaerts, J.

In: Behavioural Brain Research, Vol. 236, 01.01.2013, p. 16-22.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801

AU - Reneerkens, O.A.H.

AU - Rutten, K.

AU - Bollen, E.

AU - Hage, T.

AU - Blokland, A.

AU - Steinbusch, H.W.M.

AU - Prickaerts, J.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1 mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3 mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1 mg/kg (p.o.) in the scopolamine model and 0.3-3 mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1 mg/kg) and PQ-10 (0.3 mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1 mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement. (c) 2012 Elsevier B.V. All rights reserved.

AB - The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1 mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3 mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1 mg/kg (p.o.) in the scopolamine model and 0.3-3 mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1 mg/kg) and PQ-10 (0.3 mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1 mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement. (c) 2012 Elsevier B.V. All rights reserved.

KW - Phosphodiesterase

KW - cGMP

KW - cAMP

KW - BAY 60-7550

KW - PQ-10

KW - Object recognition

KW - Memory

KW - ACUTE TRYPTOPHAN DEPLETION

KW - LONG-TERM POTENTIATION

KW - RECOGNITION MEMORY

KW - CYCLIC-GMP

KW - PHOSPHODIESTERASE 10A

KW - IMMUNOHISTOCHEMICAL LOCALIZATION

KW - INDUCED IMPAIRMENTS

KW - PERIRHINAL CORTEX

KW - RAT HIPPOCAMPUS

KW - CGMP

U2 - 10.1016/j.bbr.2012.08.019

DO - 10.1016/j.bbr.2012.08.019

M3 - Article

VL - 236

SP - 16

EP - 22

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -