Phosphodiesterase type 5 inhibition coupled to strong reinforcement results in two periods of transient retention loss in the young chick.
Previous behavioural studies which have administered phosphodiesterase type-5 (PDE5) inhibitors have consistently demonstrated improved retention. However, when young chicks were trained on a strongly reinforced passive avoidance task 100microM zaprinast caused two periods of transient retention loss. This is opposed to past findings and may suggest an effect on retrieval. It is hypothesised that the level of reinforcement is central to this phenomenon. The molecular corollary of this may be the need to maintain cGMP homeostasis such that strong reinforcement+zaprinast may impair retention through the production of excessive levels of cGMP. This was demonstrated by two challenge studies whereby increasing concentrations of 8-Br-cGMP were administered in the presence of the guanylate cyclase inhibitor ODQ (100microM; ic) resulting in an inverted "U-shaped" retention curve. These findings suggest a more complex role for PDE5 and cGMP in memory processing than previously described and question the role of PDE5 inhibitors as nootropes under all circumstances.
Edwards
T M
TM
School of Psychology, Psychiatry and Psychological Medicine, Monash University, Wellington Rd., Clayton, Victoria 3800, Australia. tom.edwards@med.monash.edu.au
Lindley
N
N
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D002645:Chickens; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008569:Memory Disorders / Q000139:chemically induced* / Q000201:enzymology; D058986:Phosphodiesterase 5 Inhibitors; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012054:Reinforcement, Psychology; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D011688:Purinones; D011810:Quinoxalines; C016276:8-bromocyclic GMP; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C011145:zaprinast; D006152:Cyclic GMP