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Acta Psychiatr Scand. 2013 Aug;128(2):107-13. doi: 10.1111/acps.12166. Epub 2013 Jun 17.

No effect of acute tryptophan depletion on phosphodiesterase inhibition--related improvements of short-term object memory in male Wistar rats.

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  • 1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. eva.vandonkelaar@maastrichtuniversity.nl

Abstract

OBJECTIVE:

To further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD).

METHOD:

Wistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance.

RESULTS:

Although ATD significantly decreased TRP levels in the hippocampus 2 h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed.

CONCLUSION:

Changes in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KEYWORDS:

acute tryptophan depletion; phosphodiesterase inhibitors; rat object memory; serotonin

PMID:
23772681
[PubMed - indexed for MEDLINE]
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