Chronic aortic denervation decreases anxiety and impairs social memory in rats Dimitrios Kouvelas ⁎, Chryssa Pourzitaki, Georgios Papazisis, Konstantinos Tsilkos, Michail Chourdakis, Michaela M. Kraus Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, P.O. Box 1532, GR-54006, Thessaloniki, Greece abstract article info Article history: Received 14 May 2009 Accepted 2 September 2009 Keywords: Aortic denervation Anxiety Memory Behaviour Hypertension Blood pressure lability Aims: The present study investigates anxiety-like behaviour and social cognitive performance in rats with chronic aortic denervation. Main methods: The aortic depressor nerve was bilaterally transected in Wistar rats, causing an almost complete disruption of baroreceptors. Bilateral aortic denervated (bAD), sham-operated (SHAM), and intact (CTRL) rats performed an elevated plus-maze test and an olfactory social memory test, one and three months after operation. Blood pressure and heart rate were monitored in all animals. Key findings: Systolic blood pressure, blood pressure lability and heart rate were elevated in bAD rats compared to SHAM and CTRL rats. In the elevated plus-maze test, bAD rats spent clearly more time in investigating open arms and performed more open arm entries than SHAM and CTRL rats during both testing sessions. The olfactory social memory test revealed that acquisition time during first contact with a juvenile rat did not differ between the groups of rats. The recognition time spent by SHAM and CTRL group of rats was distinctly decreased in comparison to the acquisition time, an indication of social memory. bAD rats investigated the juvenile rat during the second contact to a similar extent than during the first contact, both one and three months after denervation. Significance: These results suggest that bilateral aortic denervation induces chronic neurogenic hypertension and elevated blood pressure lability, decreases anxiety-like behaviour and deteriorates social memory in rats while acquiring of social information is not affected. © 2009 Elsevier Inc. All rights reserved. Introduction Hypertension represents a major risk factor for cerebrovascular incidents, but is also associated to milder forms of brain injury. Furthermore, there is evidence that not only sustained hypertension, but also blood pressure lability plays a critical role in the development of cardiovascular diseases and organ damage (Su and Miao 2005; Parati et al. 1987; Miao et al. 2006). Studies, both in humans and animals investigate the role of hypertension on emotional and cognitive behaviour. In a study of 114 patients an association between the level of hypertension and cognitive impairment was observed, especially in reading, executive functioning, constructional, and memory-recall (Ostrosky-Solis et al. 2001). Another comparative study revealed cognitive dysfunction and increased anxiety-depressive disorders in chronic hypertensive patients (Starchina et al. 2008). Furthermore, memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow response, especially in parietal cortex (Jennings et al. 2005). The results of experimental studies in animals are controversial. Likely this discrepancy is caused, amongst others, by the use of various experimental models of hypertension resulting in a different pathophysiology of hypertension. Depending on the applied model, different raises of blood pressure values, either or not accompanied by elevated blood pressure lability and changes in heart rate, are evoked. Renovascular hypertension e.g. also leads to accumulation of metabolic products and biochemical alterations that may affect behaviour and memory. Furthermore, the results were received by using different strains of rats of different age, thus genetic variations and physiological changes during ageing such as arteriosclerosis have to be taken into consideration. The combination of different models of hypertension with a variety of behavioural, learning, and memory tasks additionally impedes comparison of the findings. For instance, renal hypertensive rats show anxiogenic-like behaviour in an elevated plus-maze test (Srinivasan et al. 2003), while spontaneous hyperten- sive rats (SHR), another model of hypertension, have decreased levels of anxiety in an open-field test (Durand et al. 1999) but also in an elevated plus-maze test (Durand et al. 1999; Takahashi et al. 2001). Furthermore, chronic hypertension evoked by aortic coarctation leads, ten months after surgery, to no impairment in spatial learning and memory when observing the rats during a repeated-acquisition water maze task (Kadish et al. 2001). On the other hand, SHR rats show deteriorated performance on learning and memory in an Life Sciences 85 (2009) 602–608 ⁎ Corresponding author. Tel./fax: +30 2310 999335. E-mail address: kouvelas@auth.gr (D. Kouvelas). 0024-3205/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2009.09.002 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie