Post-training intrahippocampal infusion of nicotine prevented spatial memory retention deficits by the Cyclooxygenase-2-specific inhibitor celecoxib in rats

M. Sharifzadeh¹, M. Tavasoli¹, N. Naghdi², A. Ghanbari¹, M. Amini¹ and A. Roghani^3,4

¹Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
²Department of Pharmacology, Iran Pasteur Institute, Tehran, Iran.
³Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, USA
⁴Texas Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, USA

In the present work, we have investigated the effects of nicotine, infused in the rat dorsal hippocampus several minutes after infusion of celecoxib, on memory retention in the Morris water maze. Rats were trained for 3 days, each day, included two blocks and each block contained 4 trials. Test trials were conducted 48 h after surgery. Bilateral intrahippocampal infusion of celecoxib (0.1 M) increased escape latency and travel distance in rats, indicating significant impairment in spatial memory retention. We also examined effects of bilateral infusion of nicotine (0.5, 1.0, and 2.0 µg/side) on memory retention. Infusion of 1 µg nicotine significantly decreased escape latency and travel distance but not swimming speed, compared to controls, suggesting memory retention enhancement by nicotine at this concentration. In separate experiments, bilateral infusion of nicotine, infused 5 min after 0.1 M celecoxib infusion, showed escape latency, travel distance and swimming speed profiles very similar to the control animals. Brain tissues from several of these animals were subjected to immunohistochemical staining analysis with anti-COX-2 antibodies. These analyses showed that COX-2 infusion alone qualitatively reduced the number and density of COX-2-containing neurons in the dorsal hippocampus, and that the immunostaining pattern was qualitively similar to controls for rats receiving a combination of celecoxib and nicotine. These results suggest that nicotine prevented or reversed the adverse effects of celecoxib on spatial memory retention and protected or restored the immunostaining pattern of COX-2 neurons in the rat dorsal hippocampus..

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.

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