en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction:</strong> It is well documented that insulin has neuroprotective and neuromodulator effects and can protect against different models of memory loss. Furthermore, cholinergic activity plays a significant role in memory, and scopolamine-induced memory loss is widely used as an experimental model of dementia. The current study aimed at investigating the possible effects of insulin against scopolamine-induced memory impairment in Wistar rat and its underlying molecular mechanisms.<br> <strong>Methods:</strong> Accordingly, animals were bilaterally cannulated in CA1, hippocampus. Intrahippocampal administration of insulin 6 MU and 12 MU in CA1 per day was performed during first 6 days after surgery. During next four days, the animal&rsquo;s spatial learning and memory were assessed in Morris water maze test (three days of learning and one day of retention test). The animals received scopolamine (1 mg/kg) Intraperitoneally (IP) 30 minutes before the onset of behavioral tests in each day. In the last day, the hippocampi were dissected and the levels of MAPK (mitogen-activated protein kinases) and caspase-3 activation were analyzed by Western blot technique.&nbsp;<br> <strong>Results:</strong> The behavioral results showed that scopolamine impaired spatial learning and memory without activating casapase-3, P38, and JNK, but chronic pretreatment by both doses of insulin was unable to restore this spatial memory impairment. In addition, scopolamine significantly reduced Extracellular signal-Regulated Kinases (ERKs) activity and insulin was unable to restore this reduction. Results revealed that scopolamine-mediated memory loss was not associated with hippocampal damage.<br> <strong>Conclusion:</strong> Insulin as a neuroprotective agent cannot restore memory when there is no hippocampal damage. In addition, the neuromodulator effect of insulin is not potent enough to overwhelm scopolamine-mediated disruptions of synaptic neurotransmission.</div> Alzheimer Disease, Cholinergic neurons, Scopolamine, Mitogen-Activated Protein Kinases, Caspase-3, Apoptosis 23 36 http://bcn.iums.ac.ir/browse.php?a_code=A-10-419-2&slc_lang=en&sid=1 Ahmad Jahanmahin ahmadjahanmahin@gmail.com 13700319475328460019304 13700319475328460019304 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Zahra Abbasnejad z.abbasnejad92@gmail.com 13700319475328460019305 13700319475328460019305 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abbas Haghparast haghparast@yahoo.com 13700319475328460019306 13700319475328460019306 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abolhassan Ahmadiani 13700319475328460019307 13700319475328460019307 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Rasoul Ghasemi r_ghasemi60@yahoo.com 13700319475328460019308 13700319475328460019308 Yes Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.