Effects of nitric oxide synthase inhibitors 1-(2-trifluoromethylphenyl)--imidazole (TRIM) and 7-nitroindazole (7-NI) on learning and memory in mice. Mutlu, O., Ulak, G., & Belzung, C. Fundamental \& Clinical Pharmacology, 25(3):368--377, June, 2011.
doi  abstract   bibtex   
Nitric oxide (NO) plays an important role in hippocampal long-term potentiation (LTP), which is involved in memory processes. This led to the hypothesis that nitric oxide synthase (NOS) inhibitors will have disturbing effects on learning and memory. The aim of our study was to investigate the effects of the new selective neuronal and inducible NOS inhibitor 1- (2-trifluoromethylphenyl) imidazole (TRIM) (10-50 mg/kg) on learning and memory and compare it to the nonselective NOS inhibitor 7-NI (15-45 mg/kg) using different behavioral tests in Swiss mice, thus clarifying the role of neuronal NOS (nNOS) and endothelial NOS (eNOS) in cognitive processes. TRIM had no specific effect on either learning or memory parameters, while 7-NI (30 mg/kg) disturbed spatial memory in the probe trial of the Morris water maze test, which was performed on the last day of the test. No differences between TRIM and the control groups were observed, while 7-NI (30 and 45 mg/kg) significantly disturbed memory in the novel object recognition test. In the social transmission of food preference test, both TRIM (50 mg/kg) and 7-NI (45 mg/kg) impaired hippocampal olfactory memory, but the total food consumption was also significantly decreased at these doses. In the passive avoidance test, TRIM did not disturb the performance, while memory impairment was observed, even with lower doses of 7-NI. All of these results suggest that TRIM has no clear effect on cognitive impairment compared to 7-NI and that inhibition of both nNOS and eNOS are necessary for the deterioration of memory processes.
@article{ mutlu_effects_2011,
  title = {Effects of nitric oxide synthase inhibitors 1-(2-trifluoromethylphenyl)--imidazole ({TRIM}) and 7-nitroindazole (7-{NI}) on learning and memory in mice},
  volume = {25},
  issn = {1472-8206},
  doi = {10.1111/j.1472-8206.2010.00851.x},
  abstract = {Nitric oxide ({NO}) plays an important role in hippocampal long-term potentiation ({LTP}), which is involved in memory processes. This led to the hypothesis that nitric oxide synthase ({NOS}) inhibitors will have disturbing effects on learning and memory. The aim of our study was to investigate the effects of the new selective neuronal and inducible {NOS} inhibitor 1- (2-trifluoromethylphenyl) imidazole ({TRIM}) (10-50 mg/kg) on learning and memory and compare it to the nonselective {NOS} inhibitor 7-{NI} (15-45 mg/kg) using different behavioral tests in Swiss mice, thus clarifying the role of neuronal {NOS} ({nNOS}) and endothelial {NOS} ({eNOS}) in cognitive processes. {TRIM} had no specific effect on either learning or memory parameters, while 7-{NI} (30 mg/kg) disturbed spatial memory in the probe trial of the Morris water maze test, which was performed on the last day of the test. No differences between {TRIM} and the control groups were observed, while 7-{NI} (30 and 45 mg/kg) significantly disturbed memory in the novel object recognition test. In the social transmission of food preference test, both {TRIM} (50 mg/kg) and 7-{NI} (45 mg/kg) impaired hippocampal olfactory memory, but the total food consumption was also significantly decreased at these doses. In the passive avoidance test, {TRIM} did not disturb the performance, while memory impairment was observed, even with lower doses of 7-{NI}. All of these results suggest that {TRIM} has no clear effect on cognitive impairment compared to 7-{NI} and that inhibition of both {nNOS} and {eNOS} are necessary for the deterioration of memory processes.},
  language = {eng},
  number = {3},
  journal = {Fundamental \& Clinical Pharmacology},
  author = {Mutlu, Oguz and Ulak, Güner and Belzung, Catherine},
  month = {June},
  year = {2011},
  pmid = {20608991},
  keywords = {Animals, Enzyme Inhibitors, Food Preferences, Hippocampus, Imidazoles, Indazoles, Learning, Locomotion, Long-Term Potentiation, Male, Maze Learning, Memory, Mice, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type {III}},
  pages = {368--377}
}

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