Blockade of GABA(B) receptors completely reverses age-related learning impairment.
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.
Lasarge
C L
CL
Department of Psychology and Faculty of Neuroscience, Texas A&M University, College Station, TX 77843-4235, USA.
Bañuelos
C
C
Mayse
J D
JD
Bizon
J L
JL
D000375:Aging / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018756:GABA Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D058788:GABA-B Receptor Antagonists; D007859:Learning Disabilities / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D010721:Phosphinic Acids / Q000494:pharmacology / Q000627:therapeutic use; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D018080:Receptors, GABA-B / Q000378:metabolism; D012903:Smell / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; C085075:CGP 55845A