Background: Hypobaric hypoxia (HH) detoriates perception, memory, judgment and attention at high altitude. Alpha 2A adrenergic agonist, guanfacine proved to be beneficial in amelioration of neurological outcomes of many neuropsychiatric disorders.
Purpose: Adrenergic dysregulation has been implicated in hypoxia induced cognitive deficits, however, efficacy of guanfacine for HH induced cognitive decline remained to be evaluated.
Methods: Rats were exposed to HH at a simulated altitude of 25,000 ft (atmospheric pressure equivalents to 282 mm Hg, PO2 59 mm Hg) for 7 days and received IM injection of either saline or guanfacine at a dose of 1 mg/kg. Adrenergic transmission was evaluated by biomarkers i.e. norepinephrine, dopamine and tyrosine hydroxylase. Dendritic morphology was studied by Golgi-Cox staining and Neurolucida neuronal tracing. Synaptic markers i.e. synaptophysin and post synaptic density proteins were evaluated. The cognitive performance was assessed by delayed alternation task using a T-Maze.
Conclusion: The study implicates a role of alpha 2A agonist, guanfacine in amelioration of HH induced cognitive decline and associated synaptic dysregulation and dendritic damage in medial prefrontal cortex.
Ethical statement: The study was approved by the Institutional Animal Ethical Committee. The guidelines of the National Institutes of Health's Guide for the Care and Use of Laboratory Animals were followed.
Source of funding: This study was funded by Defence Research and Development Organization, Ministry of Defence, Government of India and Department of Science and Technology, Government of India.