The selective 5-HT1A receptor antagonist NAD-299 increases acetylcholine release but not extracellular glutamate levels in the frontal cortex and hippocampus of awake rat |
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| Affiliation: | 1. Department of Neuroscience, Retzius väg 8, Karolinska Institutet, SE-171 77 Stockholm, Sweden;2. Department of Physiology and Pharmacology, Nanna Svartz väg 2, Karolinska Institutet, SE-171 77 Stockholm, Sweden;3. AstraZeneca R&D Södertälje, Discovery RA CNS and Pain Control, Södertälje, Sweden;1. Department of Animal Physiology, Faculty of Biology, Kharazmi (Tarbia Moallem) University, Tehran, Iran;2. Department of Biology, Faculty of Basic Sciences, Garmsar Branch, Islamic Azad University, Garmsar, Iran;3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran;5. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran;6. Institute for Cognitive Science Studies (ICSS), Tehran, Iran;1. Division of Allergy and Immunology, Children''s Hospital of Philadelphia, Philadelphia, PA;2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States;2. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, United States;3. Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, United States;4. Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164, United States;1. UMR INSERM U930, Université François Rabelais de Tours, Tours, France;2. AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC Paris 06, CNRS UMR 7371, INSERM U1146, 75013 Paris, France;3. Department of Neurology, Pitié-Salpêtrière Hospital, Sorbonne University, UMPC Paris 06, ICM, 75013 Paris, France;4. MIRCEN, CEA UMR 9199, 18 route du Panorama, 92260 Fontenay-aux-Roses, France;5. UPMC Université Paris 6, UMR-S975, CRICM-Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, Paris, France;6. CNRS, UMR 5229, Université de Lyon 1, Centre de Neurosciences Cognitives, 67 Boulevard Pinel, Cedex, 69675 Bron, France;1. Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China;2. Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China;3. Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China;4. Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China;5. State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha 410013, Hunan, China |
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| Abstract: | The effects of the HT1A receptor antagonist NAD-299 on extracellular acetylcholine (ACh) and glutamate (Glu) levels in the frontal cortex (FC) and ventral hippocampus (HPC) of the awake rats were investigated by the use of in vivo microdialysis. Systemic administration of NAD-299 (0.3; 1 and 3 µmol/kg s.c.) caused a dose-dependent increase in ACh levels in FC and HPC (peak value of 209% and 221%, respectively) and this effect was comparable to that induced by donepezil (2.63 µmol/kg s.c.). Moreover, the ACh levels in the FC increased even after repeated (14 days) treatment with NAD-299 and when NAD-299 was injected locally into the nucleus basalis magnocellularis or perfused through the microdialysis probe implanted in the cortex. In contrast, NAD-299 failed to alter the extracellular levels of glutamate after systemic (3 µmol/kg s.c.) or local (100 µM) administration. The present data support the hypothesis that cholinergic transmission in cortico-limbic regions can be enhanced via blockade of postsynaptic 5-HT1A receptors, which may underlie the proposed cognitive enhancing properties of NAD-299 in models characterized by cholinergic deficit. |
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