Microtubule disruption and cognitive defects: effect of colchicine on learning behavior in rats.
Neuropathological findings in Alzheimer's disease (AD) suggest a possible involvement of microtubule dysfunction in neurodegenerative process pathogenesis. Because microtubules have a major role in neuronal plasticity, microtubule disruption could be also directly responsible for cognitive defects in AD. We report that in rats, continuous microtubule disruption induced by chronic colchicine administration results in a dose-dependent learning deficit. In addition, retention is also impaired. These cognitive defects are specific, as chronic colchicine induces no other behavioral toxicity within the study dose range. Colchicine-induced cognitive defects resemble those of AD, which are characterised by amnesia of recent learning and loss of formerly established memories. This new procedure of pharmacologically induced cognitive impairment may prove useful, both towards understanding AD pathogenesis and towards drug screening.
Bensimon
G
G
Departement de Pharmacologie Clinique, Hôpital Pitié-Salpêtriére, Paris, France.
Chermat
R
R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D003078:Colchicine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007858:Learning / Q000187:drug effects*; D008162:Lumicolchicines / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D008162:Lumicolchicines; D003078:Colchicine