Post‐training intrahippocampal infusion of nicotine prevents spatial memory retention deficits induced by the cyclo‐oxygenase‐2‐specific inhibitor celecoxib in rats

Abstract

Recently, we demonstrated that intrahippocampal infusion of the cyclo-oxygenase (COX)-2-specific inhibitor celecoxib impaired spatial memory retention in the Morris water maze. In the present work, we 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 four trials. Test trials were conducted 48 h after surgery. As expected, bilateral intrahippocampal infusion of celecoxib (19 lg/side; 0.1 M) increased escape latency and travel distance in rats, indicating significant impairment of spatial memory retention. We also examined the effects of bilateral infusion of nicotine (0.5, 1.0 and 2.0 lg/side) on memory retention. Infusion of 1 lg nicotine significantly decreased escape latency and travel distance but not swimming speed, compared with controls, suggesting memory retention enhancement by nicotine at this concentration. In separate experiments, bilateral infusion of nicotine, infused 5 min after 0.1 M (19 lg/side) celecoxib infusion, was associated with escape latency, travel distance and swimming speed profiles very similar to those in control animals. Brain tissue sections from several of these animals were subjected to immunohistochemical staining analysis with anti-COX-2 antibodies. Quantification analysis by optical density measurements showed that the celecoxib infusion reduced the immunoreactivity of COX-2-containing neurons in the CA1 area of the hippocampus compared with controls, although this reduction was not significant. However, infusion of a combination of celecoxib and nicotine significantly increased this immunoreactivity compared with levels in control and celecoxib-infused groups. 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.

Hippocampal α4β2 Nicotinic Acetylcholine Receptor Involvement in the Enhancing Effect of Acute Nicotine on Contextual Fear Conditioning

“…However, the brain region(s) through which nicotine produces its effect on the task could not be identified from the results of the study, because systemic administration of nicotine and DH␤E will, by definition, result in the action of the drugs throughout the central and peripheral nervous systems. Thus, the results of the present research significantly extend the findings of Davis and Gould (2006) and the findings from previous studies indicating that nicotine enhances hippocampus-dependent learning and memory (Buccafusco et al, 1996;Levin et al, 1997;Gould and Wehner, 1999;Barros et al, 2004;Sharifzadeh et al, 2005) by directly demonstrating that DH␤E-sensitive nAChRs in the hippocampus are critical for the enhancing effect of the drug. DH␤E antagonizes nAChR subtypes, including ␣4␤2, ␣4␤4, ␣3␤2, ␣2␤2, and ␣2␤4 nAChRs, that bind nicotine with high affinity (Harvey et al, 1996;Khiroug et al, 2004).…”

“…However, the role of hippocampal nAChRs in the effect of acute nicotine on learning and memory has not been demonstrated directly. Equivocal results from previous studies (Barros et al, 2004;Sharifzadeh et al, 2005) indicate that the action of nicotine at hippocampal nAChRs may be sufficient to enhance learning and memory. But, it is not known whether the action of nicotine at hippocampal nAChRs is necessary for the enhancement of learning and memory.…”

Protective Effects of Chronic Lithium Treatment against Spatial Memory Retention Deficits Induced by the Protein Kinase AII Inhibitor H-89 in Rats

“…1 ). These results are similar to those obtained in our previous studies [22,[25][26][27] . Posttraining bilateral infusions of H-89 (2.5 and 5 mol/l) into the CA1 region of the hippocampus caused significant increase in escape latency ( * * * p !…”

“…We found that bilateral intrahippocampal infusion of DMSO did not induce any significant differences in escape latency, traveled distance and swimming speed, compared with saline-treated rats during the test trials. The effective use of DMSO as a vehicle has also been reported in our previous work [22,[25][26][27] . Therefore, it appears here that DMSO infusions did not cause motor disturbances or have significant effects on spatial memory parameters.…”

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

“…In agreement with human studies, there is a great body of evidence suggesting that acute nicotine augments hippocampus-dependent contextual and spatial learning and memory while not affecting hippocampus-independent subtypes of learning (e.g., cued learning) in rodents. For example, numerous studies from both our group and other laboratories showed that acute nicotine enhanced hippocampus-dependent contextual and trace fear conditioning, but not cued fear conditioning (Gould and Wehner 1999;Gould and Higgins 2003;Gould 2003a;Gould and Lommock 2003;Gould et al 2004;Wehner et al 2004;Gould 2006, 2007;Raybuck and Gould 2007;Gulick and Gould 2008;Kenney and Gould 2008;Tian et al 2011;Portugal et al 2012a, b), as well as spatial object recognition (Kenney et al 2011), spatial learning and memory in Morris water maze (Abdulla et al 1996;Sharifzadeh et al 2005), and spatial working memory in radial arm maze tasks (Levin and Torry 1996;Levin et al 1997Levin et al , 1998. It is possible that the formation of nicotine-context associations may benefit from these procognitive effects of acute nicotine.…”