Histological and behavioral protection by (-)-nicotine against quinolinic acid-induced neurodegeneration in the hippocampus.
Injections of quinolinic acid (60, 180, and 600 nmol) in the dorsal hippocampus induced significant neurotoxicity that was evident 1 day after the injection. By day 3, pyramidal as well as granular cells were affected even at the lowest dose of quinolinic acid, an effect that persisted up to 20 days. Consistent with the histological findings, animals with bilateral injections in the dorsal hippocampus were cognitively impaired during acquisition and retention of spatial information in the water maze. A subacute treatment with (-)-nicotine (62 micromol/kg/day) delivered by subcutaneous minipumps prevented the histological and cognitive deficits induced by the bilateral quinolinic acid (60 nmol) injections. These data indicate that quinolinic acid can induce degeneration of both pyramidal as well as granule cells in the hippocampus, leading to cognitive impairments in the rat, and that activation of neuronal nicotinic acetylcholine receptors can prevent the neurodegenerative process induced by quinolinic acid.
O'Neill
A B
AB
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, 60064-3500, USA.
Morgan
S J
SJ
Brioni
J D
JD
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D017378:Quinolinic Acid / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D051381:Rats; D013037:Spatial Behavior / Q000187:drug effects*
D018696:Neuroprotective Agents; D009538:Nicotine; D017378:Quinolinic Acid