Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning

Bernabeu, Ramón; Schmitz, Paulo K.; Faillace, María Paula; Izquierdo, Iván; Medina, Jorge H.

doi:10.1097/00001756-199601310-00050

Cited by 144 publications

(95 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first one was at 0 h after training and coincided with the early labile phase of memory (7). The second one (3 to 6 h) coincided with an increase in cAMP (3,5), PKA activity (3,5) and CREB-P levels (3) described in the hippocampus following training in this task. This second "window" slightly precedes a peak of hippocampal glycoprotein synthesis (8) and ultrastructural changes in the dentate gyrus (6) observed after similar tasks.…”

Section: Bevilaqua Et Almentioning

confidence: 70%

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Bevilaqua

Ardenghi

Schröder

et al. 1997

Braz J Med Biol Res

View full text Add to dashboard Cite

Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 µg/side), SCH23390 (0.5 µg/side), norepinephrine (0.3 µg/side), timolol (0.3 µg/side), 8-OH-DPAT (2.5 µg/side), NAN-190 (2.5 µg/side), forskolin (0.5 µg/side), KT5720 (0.5 µg/side) or 8-Br-cAMP (1.25 µg/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-BrcAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D 1 , ß, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.Correspondence

show abstract

Section: Bevilaqua Et Almentioning

confidence: 70%

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Bevilaqua

Ardenghi

Schröder

et al. 1997

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…However, this is not necessarily the case, since the measurements of the memory improvement in the passive avoidance task are influenced by many different factors, such as species-dependent differences in sensitivity to drug treatment. Nevertheless, evidence is accumulating that PDE5 inhibition and cGMP are involved in processes of early consolidation of electric shock and object information (see also Bernabeu et al 1996Bernabeu et al , 1997Prickaerts et al 1997Prickaerts et al , 2002a.…”

Section: Pde5 Inhibition and Object Recognition Memorymentioning

confidence: 99%

“…In addition, it has been found that injections of 8-bromo-cGMP into the hippocampus immediately after the first trial improved the memory performance in both the object recognition (Prickaerts et al 2002a) and passive avoidance task (Bernabeu et al 1996). Sildenafil has been demonstrated to penetrate the brain (FDA 1998).…”

Section: Effects Of Both Drug Classes On Exploratory Activitymentioning

confidence: 99%

Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

Prickaerts

Şık

Staay³

et al. 2004

Psychopharmacology

126

View full text Add to dashboard Cite

Rationale: Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes.Objective: We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. Methods: The object recognition task measures whether rats remembered an object they have explored in a previous learning trial. All drugs were given orally 30 min before or immediately after learning to study acquisition and consolidation, respectively. Results: Sildenafil given immediately after the first trial improved the memory performance after 24 h and resulted in an inverted U-shaped dose-effect curve with the peak dose at 3 mg/kg. When given before the first trial, sildenafil also improved the memory performance. However, the dose needed for the best performance under this condition was 10 mg/kg, suggesting that the dose-effect curve shifted to the right. This can be explained by the metabolic clearance of the high dose of sildenafil. Donepezil had no memory improving effect when given after the first trial. However, when given before the first trial, a gradually increasing dose-effect curve was found which had its maximum effect at the highest dose tested (1 mg/kg). Likewise, only when metrifonate (30 mg/kg) was given before the first trial did rats show an improved memory performance. Conclusion: Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information.

show abstract

“…Three promising targets through which memory improvement may be effected are cAMP-selective PDE4 (Barad et al, 1998;Rose et al, 2005;Rutten et al, 2007a;Zhang et al, 2005); cGMP-selective PDE5 (Prickaerts et al, 2004;Rutten et al, 2005); and PDE2, which hydrolyzes both cAMP and cGMP (Boess et al, 2004;Rutten et al, 2007b;Van Donkelaar et al, 2008). Evidence is accumulating that second messenger molecules, cGMP and cAMP, are important in memory processes in general and long-term potentiation in particular (Bach et al, 1999;Bernabeu et al, 1996;Bourtchouladze et al, 1998;Frey et al, 1993;Lu et al, 1999;Prickaerts et al, 2002a;Son et al, 1998). We have previously shown that PDE4, PDE5, and PDE2 inhibitors all improved the performance of rodents in an object recognition task (ORT) and the timedependent effects of cGMP-or cAMP-selective PDE inhibitors suggested that cGMP was mainly involved in early phase consolidation processes and cAMP in late phase consolidation processes (Rutten et al, 2007b).…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase Inhibitors Enhance Object Memory Independent of Cerebral Blood Flow and Glucose Utilization in Rats

Rutten

Donkelaar

Ferrington

et al. 2009

Neuropsychopharmacol

113

View full text Add to dashboard Cite

Phosphodiesterase (PDE) inhibitors prevent the breakdown of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), and are currently studied as possible targets for cognitive enhancement. Earlier studies indicated beneficial effects of PDE inhibitors in object recognition. In this study we tested the effects of three PDE inhibitors on spatial memory as assessed in a place and object recognition task. Furthermore, as both cAMP and cGMP are known vasodilators, the effects of PDE inhibition on cognitive functions could be explained by enhancement of cerebrovascular function. We examined this possibility by measuring the effects of PDE5 and PDE4 inhibitor treatment on local cerebral blood flow and glucose utilization in rats using [ 14 C]-iodoantipyrine and [ 14 C]-2-deoxyglucose quantitative autoradiography, respectively. In the spatial location task, PDE5 inhibition (cGMP) with vardenafil enhanced only early phase consolidation, PDE4 inhibition (cAMP) with rolipram enhanced only late phase consolidation, and PDE2 inhibition (cAMP and cGMP) with Bay 60-7550 enhanced both consolidation processes. Furthermore, PDE5 inhibition had no cerebrovascular effects in hippocampal or rhinal areas. PDE4 inhibition increased rhinal, but not hippocampal blood flow, whereas it decreased glucose utilization in both areas. In general, PDE5 inhibition decreased the ratio between blood flow and glucose utilization, indicative of general oligaemia; whereas PDE4 inhibition increased this ratio, indicative of general hyperemia. Both oligaemic and hyperemic conditions are detrimental for brain function and do not explain memory enhancement. These results underscore the specific effects of cAMP and cGMP on memory consolidation (object and spatial memory) and provide evidence that the underlying mechanisms of PDE inhibition on cognition are independent of cerebrovascular effects.

show abstract

Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning

Cited by 144 publications

References 0 publications

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

Phosphodiesterase Inhibitors Enhance Object Memory Independent of Cerebral Blood Flow and Glucose Utilization in Rats

Contact Info

Product

Resources

About