Inhibition of guanylate cyclase and protein kinase G impairs retention for the passive avoidance task in the day-old chick.
Nitric oxide (NO) is a highly labile chemical messenger which has previously been implicated in memory processes in a variety of learning paradigms and species. However, there is only limited evidence to suggest which enzymes are acted upon by NO during the formation of memory. The present study investigates the role of guanylate cyclase (GC) and protein kinase G (PKG) in a form of passive avoidance learning known to be dependent on nitric oxide activity. It was determined that in vivo pharmacological inhibition of GC using either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one or 6-anilino-5,8-quinolinedione resulted in two transitory memory retention deficits centred around 40 and 120 min posttraining, respectively. In contrast, inhibition of PKG with N-[2-(methylamino)ehtyl]-5-isoquinoline-sulfornamide hydrochloride (H-8) resulted in a single temporary retention loss centered at 120 min posttraining. These temporary retention losses appear to be specific to memory since they were dose-dependent and could not be explained by nonspecific performance effects. Further, these results suggest that these agents inhibit memory retrieval rather than formation, since memory is subsequently available. The current findings indicate that guanylyl cyclase mediates two memory retrieval processes, the latter of which appears to be PKG-dependent. In contrast, since inhibition of NO results in a permanent retention loss, it is suggested that NO is required for memory formation through GC-independent processes.
Edwards
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TM
Department of Psychology, Monash University, Caulfield East, Victoria 3800, Australia.
Rickard
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NS
Ng
K T
KT
D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects*; D002645:Chickens; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D010069:Oxadiazoles / Q000009:adverse effects; D011897:Random Allocation; D012153:Retention, Psychology / Q000187:drug effects*; D013997:Time Factors
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase