Prolonged exposure to cigarette smoke blocks the neurotoxicity induced by kainic acid in rats.
We examined the effects of cigarette smoke (CS) on three parameters associated with kainic acid (KA)-induced neurotoxicity: seizure activity, cell loss in the hippocampus, and increased Fos-related antigen (FRA) expression. Animals were exposed to the main stream of CS from 15 Kentucky 2R1F research cigarettes containing 28.6 mg tar and 1.74 mg nicotine per cigarette, for 10 min a day, 6 days per week, for 4 weeks, using an automatic smoking machine. KA administration (10 mg/kg, i.p.) produced robust behavioral convulsions lasting 4-5 h. Pre-exposure to CS significantly reduced the seizures, mortality, and severe loss of cells in regions CA1 and CA3 of the hippocampus after KA administration. Consistently, pre-exposure to CS significantly attenuated the KA-induced increased FRA immunoreactivity in the hippocampus. In contrast, pretreatment with central nicotinic antagonist, mecamylamine (2 or 10 mg/kg, i.p.) blocked the neuroprotective effects mediated by CS in a dose-dependent manner. These results indicate that CS exposure provides neuroprotection against the KA insult via nicotinic receptor activation.
Kim
H C
HC
Department of Pharmacy, College of Pharmacy, Kangwon National University, Korea Institute of Drug Abuse, Chunchon. kimhc@cc.kangwon.ac.kr
Jhoo
W K
WK
Ko
K H
KH
Kim
W K
WK
Bing
G
G
Kwon
M S
MS
Shin
E J
EJ
Suh
J H
JH
Lee
Y G
YG
Lee
D W
DW
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D010947:Plants, Toxic; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D012906:Smoke; D014026:Nicotiana
D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D012906:Smoke; D008464:Mecamylamine; D009538:Nicotine; D007608:Kainic Acid