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

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