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Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats

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Abstract

Rational

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.

Conclusion

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.

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Acknowledgments

Financial support to Santoshkumar Tota from the Council of Scientific and Industrial Research (CSIR) New Delhi, India, is gratefully acknowledged.

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Authors and Affiliations

  1. Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

    Santoshkumar Tota, Ruby Goel, Rajasekar N. & Kashif Hanif

  2. Division of Pharmaceutics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

    Shakti Deep Pachauri

  3. Division of Toxicology, CSIR-Central Drug Research Institute, Chattar Manzil Palace, Lucknow, Uttar Pradesh, India

    Chandishwar Nath

  4. Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

    Santoshkumar Tota & Abul Kalam Najmi

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  1. Santoshkumar Tota
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  2. Ruby Goel
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Correspondence to Chandishwar Nath.

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Tota, S., Goel, R., Pachauri, S.D. et al. Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats. Psychopharmacology 226, 357–369 (2013). https://doi.org/10.1007/s00213-012-2913-8

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  • DOI: https://doi.org/10.1007/s00213-012-2913-8

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