title: Effects of Antecedent GABA A Receptor Activation on Counterregulatory Responses to Exercise in Healthy Man.
abstract: The aim of this study was to determine whether antecedent stimulation of γ-aminobutyric acid (GABA) A receptors with the benzodiazepine alprazolam can blunt physiologic responses during next-day moderate (90 min) exercise in healthy man. Thirty-one healthy individuals (16 male/15 female aged 28 ± 1 year, BMI 23 ± 3 kg/m(2)) were studied during separate, 2-day protocols. Day 1 consisted of morning and afternoon 2-h hyperinsulinemic-euglycemic or hypoglycemic clamps with or without 1 mg alprazolam given 30 min before a clamp. Day 2 consisted of 90-min euglycemic cycling exercise at 50% VO2max. Despite similar euglycemia (5.3 ± 0.1 mmol/L) and insulinemia (46 ± 6 pmol/L) during day 2 exercise studies, GABA A activation with alprazolam during day 1 euglycemia resulted in significant blunting of plasma epinephrine, norepinephrine, glucagon, cortisol, and growth hormone responses. Lipolysis (glycerol, nonesterified fatty acids) and endogenous glucose production during exercise were also reduced, and glucose infusion rates were increased following prior euglycemia with alprazolam. Prior hypoglycemia with alprazolam resulted in further reduction of glucagon and cortisol responses during exercise. We conclude that prior activation of GABA A pathways can play a significant role in blunting key autonomous nervous system, neuroendocrine, and metabolic physiologic responses during next-day exercise in healthy man.
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Maka S
authors.initials: MS
authors.lastname: Hedrington
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Younk
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD sdavis@medicine.umaryland.edu.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001642:Bicycling / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D019382:Human Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D000525:Alprazolam