title: Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats.
abstract: BACKGROUND
  Studies have shown the involvement of angiotensin II (Ang II) in neurobehavioral aspects, but the exact role of Ang II in memory is still ambiguous.
  
  
  OBJECTIVE
  This study explored the effect of central Ang II on spatial memory along with cholinergic neurotransmission, brain energy metabolism, cerebral blood flow (CBF), and brain-derived neurotrophic factor (BDNF) in rats.
  
  
  METHODS
  Spatial memory was evaluated by Morris water maze (MWM) after Ang II (ICV) administration in male Sprague-Dawley rats. CBF was measured by laser Doppler flowmetry. Oxidative stress adenosine triphosphate (ATP), BDNF, acetylcholinesterase (AChE), and acetylcholine (ACh) were estimated in the cortex and hippocampus at 1, 24, and 48 h after Ang II administration. The effect of AT1 and AT2 receptor blocker (candesartan and PD123,319, respectively), AChE inhibitor (donepezil), and antioxidant melatonin was studied on memory, CBF, and biochemical parameters.
  
  
  RESULTS
  Ang II caused spatial memory impairment by affecting acquisition, consolidation, and recall in the MWM test along with a significant reduction in CBF. Ang II significantly reduced ACh level and caused oxidative stress in the rat brain 1 h post-injection. No significant change was observed in BDNF, AChE, and ATP level. Candesartan and donepezil prevented Ang II-induced memory impairment, reduction in CBF and ACh level. However, PD123,319 and melatonin failed to prevent Ang II-induced memory impairment but improved CBF partially.
  
  
  CONCLUSIONS
  This study suggests that Ang II, via the AT1 receptor, affects spatial memory formation, CBF, and ACh level while AT2 receptor has no significant role.
authors.affiliation: Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Santoshkumar
authors.initials: S
authors.lastname: Tota
authors.forename: Ruby
authors.initials: R
authors.lastname: Goel
authors.forename: Shakti Deep
authors.initials: SD
authors.lastname: Pachauri
authors.forename: N
authors.initials: N
authors.lastname: Rajasekar
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D006624:Hippocampus / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008568:Memory / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D019208:Brain-Derived Neurotrophic Factor; D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D007189:Indans; D010880:Piperidines; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000255:Adenosine Triphosphate; D000077265:Donepezil; D000110:Acetylcholinesterase; D008550:Melatonin; D000109:Acetylcholine; C081643:candesartan