NPY Y 1 and Y 2 receptors in the regulation of mouse recognition and procedural memory: Interplay with cellular signalling, noradrenergic transmission and monoamine concentrations
Background and Purpose
Recognition and procedural memory are modulated by the noradrenergic system, whose terminals release noradrenaline along with neuropeptide Y, acting via Y1 and Y2 receptors. This study aims to investigate the role of Y1 and Y2 receptor antagonists (BMS‐193885 and SF‐11) on recognition and procedural memory, including their co‐administration with clenbuterol, a β
2
‐adrenoceptor agonist, with additional focus on the molecular mechanisms underlying memory‐related behavioural changes.
Experimental Approach
Recognition memory was assessed in mice using the novel object recognition task. Motor learning and procedural memory were evaluated in the accelerating rotarod test. Memory‐related behavioural outcomes were complemented by analyses of NPY levels, the phosphorylation status of CaMKII and ERK1/2, along with the concentrations of 5‐HT, dopamine, noradrenaline and its metabolite in selected brain regions, including the prefrontal cortex, hippocampus and cerebellum.
Key Results
SF‐11 at 5 mg·kg
−1
impaired recognition memory, prolonged procedural memory retention and inhibited CaMKII, but at 20 mg·kg
−1
, SF‐11 disrupted both recognition and procedural memory increasing NPY. BMS‐193885, at 5 mg·kg
−1
, prolonged procedural memory retention, but at 20 mg·kg
−1
, it impaired long‐term recognition memory, prolonged procedural memory retention, increased NPY and decreased phospho‐CaMKII. Clenbuterol enhanced procedural memory retention, but this pro‐cognitive effect was diminished by co‐administration with either Y receptor antagonist, which correlated with decreased noradrenaline levels.
Conclusions and Implications
NPY receptor antagonists modulate memory processes in a dose‐ and memory‐type‐dependent manner, and these effects appear to be linked to hippocampal function. NPY receptors may serve as therapeutic targets to treat cognitive impairments.
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- Published
- Dec 08, 2025
- Vol/Issue
- 183(9)
- Pages
- 1958-1974
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