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Bilateral ischaemic lesions of the medial prefrontal cortex are anxiogenic in the rat

Published online by Cambridge University Press:  05 December 2017

Robert A. Déziel
Affiliation:
Department of Biomedical Sciences, University of Prince Edward Island, Canada
R. Andrew Tasker*
Affiliation:
Department of Biomedical Sciences, University of Prince Edward Island, Canada Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark
*
R. Andrew Tasker, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI, Canada C1A 4P3. Tel: +1-902-566-0662; Fax: +1-902-566-0832; E-mail: [email protected]

Abstract

Objective

Stroke patients often suffer from delayed disturbances of mood and cognition. In rodents, the prefrontal cortex (PFC) is involved in both higher order cognition and emotion. Our objective was to determine if bilateral focal ischaemic lesions restricted to the medial prefrontal cortex (mPFC) could be used to model post-stroke anxiety and/or cognitive deficits.

Methods

Groups of adult male Sprague-Dawley rats (n=9) received bilateral injections of either endothelin-1 (ET-1) (400 pmol) or vehicle (artificial cerebrospinal fluid) into the mPFC and were tested at various times using both a test of temporal order memory and in an elevated plus maze. Lesions were verified histologically.

Results

ET-1 lesioned rats had reduced mobility on post-surgery day 8 that had resolved by day 29 at which time they spent significantly more time in the closed arm of the plus maze

Conclusion

We conclude that ischaemic lesions localised to the mPFC can be used to model post-stroke anxiety in rats.

Type
Short Communication
Copyright
© Scandinavian College of Neuropsychopharmacology 2017 

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References

1. Strong, K, Mathers, C, Bonita, R. Preventing stroke: saving lives around the world. Lancet Neurol 2007;6:182187.Google Scholar
2. Kleim, JA, Boychuk, JA, Adkins, DL. Rat models of upper extremity impairment in stroke. ILAR J 2007;48:374384.Google Scholar
3. Tatemichi, TK, Desmond, DW, Stern, Y, Paik, M, Sano, M, Bagiella, E. Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatry 1994;57:202207.Google Scholar
4. Liu, F, McCullough, LD. Middle cerebral artery occlusion model in rodents: methods and potential pitfalls. J Biomed Biotechnol 2011;2011:464701.Google Scholar
5. Sharkey, J, Butcher, SP. Characterisation of an experimental model of stroke produced by intracerebral microinjection of endothelin-1 adjacent to the rat middle cerebral artery. J Neurosci Methods 1995;60:125131.Google Scholar
6. Luscher, TF, Barton, M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000;102:24342440.Google Scholar
7. Thiyagarajan, M, Sharma, SS. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 2004;74:969985.Google Scholar
8. Livingston-Thomas, JM, McGuire, EP, Doucette, TA, Tasker, RA. Voluntary forced use of the impaired limb following stroke facilitates functional recovery in the rat. Behav Brain Res 2014;261:210219.Google Scholar
9. Birrell, JM, Brown, VJ. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 2000;20:43204324.Google Scholar
10. Espejo, EF. Selective dopamine depletion within the medial prefrontal cortex induces anxiogenic-like effects in rats placed on the elevated plus maze. Brain Res 1997;762:281284.Google Scholar
11. Bissiere, S, McAllister, KH, Olpe, H-R, Cryan, JF. The rostral anterior cingulate cortex modulates depression but not anxiety-related behaviour in the rat. Behav Brain Res 2006;175:195199.Google Scholar
12. Paxinos, G, Watson, C. The rat brain in stereotaxic coordinates. 6th edn. Academic Press, London UK. 2007.Google Scholar
13. Hannesson, DK, Howland, JG, Phillips, AG. Interaction between perirhinal and medial prefrontal cortex is required for temporal order but not recognition memory for objects in rats. J Neurosci 2004;24:45964604.Google Scholar
14. Jiwa, NS, Garrard, P, Hainsworth, AH. Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem 2010;115:814828.Google Scholar
15. Butler, TL, Kassed, CA, Sanberg, PR, Willing, AE, Pennypacker, KR. Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion. Brain Res 2002;929:252260.Google Scholar
16. Hartman, RE, Lee, JM, Zipfel, GJ, Wozniak, DF. Characterizing learning deficits and hippocampal neuron loss following transient global cerebral ischemia in rats. Brain Res 2005;1043:4856.Google Scholar
17. Uylings, HBM, Groenewegen, HJ, Kolb, B. Do rats have a prefrontal cortex? Behav Brain Res 2003;146:317.Google Scholar
18. Salzman, CD, Fusi, S. Emotion, cognition, and mental state representation in amygdala and prefrontal cortex. Annu Rev Neurosci 2010;33:173202.Google Scholar
19. Kolb, B, Nonneman, AJ. Frontolimbic lesions and social behavior in the rat. Physiol Behav 1974;13:637643.Google Scholar
20. Giancola, PR. EVidence for dorsolateral and orbital prefrontal cortical involvement in the expression of aggressive behavior. Aggress Behav 1995;21:431450.Google Scholar
21. Livingston-Thomas, JM, Jeffers, MS, Nguemeni, C, Shoichet, MS, Morshead, CM, Corbett, D. Assessing cognitive function following medial prefrontal stroke in the rat. Behav Brain Res 2015;294:102110.Google Scholar
22. Shah, AA, Treit, D. Excitotoxic lesions of the medial prefrontal cortex attenuate fear responses in the elevated-plus maze, social interaction and shock probe burying tests. Brain Res 2003;969:183194.Google Scholar
23. Motzkin, JC, Philippi, CL, Wolf, RC, Baskaya, MK, Koenigs, M. Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol Psychiatry 2015;77:276284.Google Scholar
24. File, SE. One-trial tolerance to the anxiolytic effects of chlordiazepoxide in the plus-maze. Psychopharmacology (Berl) 1990;100:281282.Google Scholar
25. Barker, GRI, Bird, F, Alexander, V, Warburton, EC. Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci 2007;27:29482957.Google Scholar