Abstract
BackgroundWe aimed to further understand the relationship between cAMP concentration and mnesic performance.Methods and FindingsRats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p.), rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p.) and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p.) before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices) before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold), prefrontal (1.3 fold) and perirhinal (1.3 fold) cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold) from drug-treated rats (except for milrinone+RS 67333 treatment). After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold) and the perirhinal cortex (2.1 fold) from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold) and milrinone (respectively 1.46 fold and 1.56 fold)-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h).ConclusionsOur results strongly suggest that a “pre-sample” early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.
Highlights
Most modern theories of learning and memory postulate that memory processes require cyclic adenosine monophosphate synthesis [1]; there is little evidence concerning the mechanisms by which memory affects adenylyl cyclase activity and/or phosphodiesterase (PDE) activity
Our results strongly suggest that a ‘‘pre-sample’’ early increase in cyclic adenosine monophosphate (cAMP) levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay
We show that a ‘‘pre-sample’’ early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay
Summary
Most modern theories of learning and memory postulate that memory processes require cyclic adenosine monophosphate (cAMP) synthesis [1]; there is little evidence concerning the mechanisms by which memory affects adenylyl cyclase activity (cAMP synthesis) and/or phosphodiesterase (PDE) activity (cAMP degradation). Several studies argue that artificial cAMP-PKA cascade activation through intra-hippocampal infusion of 8BrcAMP, adenylyl cyclase or PKA activation improves memory performance [4,6,7,8,9] whereas pharmacological inhibition of PKA disrupts hippocampal long term potentiation and hippocampusbased long-term memory [6,10,11]. Increasing PKA activity impairs prefrontal cortex-dependent memory in mice and expression of a constitutively active isoform of the G-protein subunit Gas impairs mice behavioural performance in a fearconditioning task [14]. These works clearly demonstrate the complexity of cAMP-dependent responses. We aimed to further understand the relationship between cAMP concentration and mnesic performance
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