title: No effect of acute tryptophan depletion on phosphodiesterase inhibition--related improvements of short-term object memory in male Wistar rats.
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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department 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
authors.forename: E L
authors.initials: EL
authors.lastname: van Donkelaar
authors.forename: J
authors.initials: J
authors.lastname: Prickaerts
authors.forename: S
authors.initials: S
authors.lastname: Akkerman
authors.forename: K
authors.initials: K
authors.lastname: Rutten
authors.forename: H W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: A
authors.initials: A
authors.lastname: Blokland
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004035:Diet Therapy / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000628:therapy*; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis*; D013450:Sulfones / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014227:Triazines / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism*; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D012701:Serotonin; D000069058:Vardenafil Dihydrochloride; D014364:Tryptophan
keywords: acute tryptophan depletion; phosphodiesterase inhibitors; rat object memory; serotonin