Repeated intracerebroventricular infusion of nicotine prevents kainate-induced neurotoxicity by activating the alpha7 nicotinic acetylcholine receptor.
We examined whether (-)-nicotine infusion can affect kainic acid (KA)-induced neurotoxicity in rats. Although treatment with a single nicotine infusion (0.5 or 1.0 microg/side, i.c.v.) failed to attenuate KA-induced neurotoxicity, repeated nicotine infusions (1.0 microg/side/day for 10 days) attenuated the seizures, the severe loss of cells in hippocampal regions CA1 and CA3, the increase in activator protein (AP)-1 DNA binding activity, and mortality after KA administration. alpha-Bungarotoxin and mecamylamine blocked the neuroprotective effects of nicotine. These results suggest that repeated nicotine treatment provides alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against KA toxicity.
Shin
Eun-Joo
EJ
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
Chae
Jong Seok
JS
Jung
Myung-Eun
ME
Bing
Guoying
G
Ko
Kwang Ho
KH
Kim
Won-Ki
WK
Wie
Myung Bok
MB
Cheon
Mi-Ae
MA
Nah
Seung-Yeol
SY
Kim
Hyoung-Chun
HC
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007276:Injections, Intraventricular; D007608:Kainic Acid; D007696:Kindling, Neurologic; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D018808:Transcription Factor AP-1; D064569:alpha7 Nicotinic Acetylcholine Receptor; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine; D004247:DNA; D007608:Kainic Acid