en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article <div style="text-align: justify;"><span style="line-height:1.5;"><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction: </strong>While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. Some studies suggest that NPY may also play a role in autophagy. In our investigation, we aimed to explore whether NPY and its Y2 receptor inhibitor could influence memory modulation or affect Beclin-1 expression in a rat model of Alzheimer&rsquo;s disease (AD). NPY may also have a role in autophagy, according to some studies.<br /> <strong>Methods: </strong>Intracerebroventricular (i.c.v) injections of amyloid-beta (A&beta;1-42, 2&micro;g/&micro;l/ side) were used to establish an animal model of AD. NPY (10 ng/&micro;l, 10 &micro;l, i.c.v) was administered 30 minutes before the retrieval. Y2 antagonist BIIE-0246 was injected 15 minutes before NPY administration in the targeted groups. BIIE-0246 was used at three different concentrations (20 nM, 200 nM, and 2 &micro;M). Passive avoidance memory and novel object recognition were both evaluated. Subsequently, Beclin-1 protein expression in the hippocampus was determined using western blot analysis.<br /> <strong>Results: </strong>It was found that NPY administration improved passive avoidance and cognitive memory in animals treated with A&beta;. Injecting BIIE-0246 before NPY did not reverse the improving effect of NPY on passive avoidance and Novel Object Recognition memories. Furthermore, compared to sham-operated animals, A&beta; treatment significantly reduced the hippocampal expression of Beclin-1 protein (P&le;0.05), and neither NPY nor NPY Y2 receptor inhibitors affected Beclin-1. </span></span></span></div> <span style="line-height:1.5;"><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Conclusion: </strong>In A&beta;-induced memory impairment, it is thought that NPY can improve both aversive and cognitive memory. Blocking NPY Y2 receptors with BIIE-0246 did not alter NPY&rsquo;s memory-enhancing effect</span></span></span> Neuropeptide Y, Neuropeptide Y2 receptor, Memory, Alzheimer’s disease 117 127 http://ppj.phypha.ir/browse.php?a_code=A-10-656-3&slc_lang=en&sid=1 Esfandiar Esfaniari esfaniari.esfandiar19971997@gmail.com 3200319475328460035721 3200319475328460035721 No Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Ali Hosseinkhani alihosseinkhany@gmail.com 3200319475328460035722 3200319475328460035722 No Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Samira Rashtiani sa.rashtiani67@gmail.com 3200319475328460035723 3200319475328460035723 No Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Kambiz Rohampour rohampour@gmail.com 3200319475328460035724 000000022301091X No Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Adele Jafari jafari.adele@gmail.com 3200319475328460035725 0000000234125456 Yes Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran