the effect of intrahippocampal insulin injection on scopolamine-induced spatial memory impairment and extracellular signal-regulated kinases alteration

Introduction: 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 scopolamineinduced memory loss is widely used as an experimental model of dementia. the current study aimed at investigating the possible effects of insulin against scopolamineinduced memory impairment in wistar rat and its underlying molecular mechanisms.methods: 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 (mitogenactivated protein kinases) and caspase3 activation were analyzed by western blot technique. results: the behavioral results showed that scopolamine impaired spatial learning and memory without activating casapase3, 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 signalregulated kinases (erks) activity and insulin was unable to restore this reduction. results revealed that scopolaminemediated memory loss was not associated with hippocampal damage.conclusion: 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 scopolaminemediated disruptions of synaptic neurotransmission.