Blockade of GABA(B) receptors completely reverses age-related learning impairment

• Published in: Neuroscience Vol. 164; no. 3; pp. 941 - 947
• Main Authors: Lasarge, C.L., Bañuelos, C., Mayse, J.D., Bizon, J.L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.12.2009; Elsevier
• Subjects: aging; Aging - metabolism; Aging - psychology; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; CGP55845; cognitive enhancement; Discrimination Learning - drug effects; Discrimination Learning - physiology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; GABA Antagonists - pharmacology; GABA Antagonists - therapeutic use; GABA(B) receptor; GABA-B Receptor Antagonists; learning; Learning Disabilities - drug therapy; Learning Disabilities - metabolism; Learning Disabilities - physiopathology; Male; Memory Disorders - drug therapy; Memory Disorders - metabolism; Memory Disorders - physiopathology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurology; Neuropsychological Tests; odor; Phosphinic Acids - pharmacology; Phosphinic Acids - therapeutic use; Propanolamines - pharmacology; Propanolamines - therapeutic use; Rats; Rats, Inbred F344; Receptors, GABA-B - metabolism; Smell - drug effects; Smell - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Treatment Outcome; Vertebrates: nervous system and sense organs; AChE; SD; MCI; GABA(B) receptor; learning; aging; odor; CGP55845; cognitive enhancement; mild cognitive impairments; acetylcholinesterase; standard deviation; Learning; Senescence; Acquisition process; Cognition; Gabaergic receptor B; Odor; Age
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.08.055

Impaired cognitive functions are well-described in the aging process. GABA(B) antagonists can facilitate learning and memory in young subjects, but these agents have not been well-characterized in aging. Here we show a complete reversal of olfactory discrimination learning deficits in cognitively-impaired aged Fischer 344 rats using the GABA(B) antagonist CGP55845, such that drug treatment restored performance to that on par with young and cognitively-unimpaired aged subjects. There was no evidence that this improved learning was due to enhanced olfactory detection abilities produced by the drug. These results highlight the potential of targeting GABA(B) receptors to ameliorate age-related cognitive deficits and demonstrate the utility of olfactory discrimination learning as a preclinical model for testing novel therapies to improve cognitive functions in aging.