Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits

• Published in: Physiology & behavior 2014-01, Vol.123, p.187-192
• Main Authors: Kauser, H, Sahu, S, Kumar, S, Panjwani, U
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists - therapeutic use; Analysis of Variance; Animals; Apoptosis; Apoptosis - drug effects; Behavioral psychophysiology; Biological and medical sciences; DNA Fragmentation - drug effects; Fundamental and applied biological sciences. Psychology; Guanfacine; Guanfacine - therapeutic use; Hypobaric hypoxia; Hypoxia - complications; Male; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory, Short-Term - drug effects; Nerve Degeneration - drug therapy; Nerve Degeneration - etiology; Neurodegeneration; Prefrontal cortex; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Space Perception - drug effects; Spatial working memory; Time Factors
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2013.10.028

Abstract Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000 ft for 7 days in an animal decompression chamber and received daily treatment of GFC at a dose of 1 mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7 days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH.