Mechanism of colchicine impairment on learning and memory, and protective effect of CGP36742 in mice.
Fourteen days after hippocampal microinfusion with colchicine (COL), learning and memory ability of mice was significantly impaired, while glutamate (Glu), gamma-aminobutyric acid (GABA), Glu/GABAB and GABAB receptor levels in the cortex and/or the hippocampus were significantly changed. After treatment with a GABAB receptor antagonist, CGP36742, learning and memory impairment caused by COL could be significantly improved, and the above indices in brain regions reversed. These results suggest GABAB antagonists may have therapeutic value in the treatment of Alzheimer's disease.
Yu
Z
Z
Department of Pharmacology, Sun Yat-sen University of Medical Sciences, Guangzhou, People's Republic of China. smulib@public.sta.net.cn
Cheng
G
G
Hu
B
B
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003078:Colchicine / Q000633:toxicity*; D004597:Electroshock; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007263:Infusions, Parenteral; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011869:Radioligand Assay; D011930:Reaction Time; D018080:Receptors, GABA-B / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D018696:Neuroprotective Agents; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003078:Colchicine