Acute nicotine reduces brain arachidonic acid signaling in unanesthetized rats.
Nicotine exerts its central effects by activating pre- and postsynaptic nicotinic acetylcholine receptors (nAChRs). Presynaptic nAChRs modulate the release of many neurotransmitters that bind to postsynaptic receptors. These may be coupled to the activation of cytosolic phospholipase A(2) (cPLA(2)), which hydrolyzes arachidonic acid (AA) from membrane phospholipids. We hypothesized that nicotine would modify brain signaling involving AA by binding to nAChRs. Nicotine (0.1 mg/kg, subcutaneously) or saline was injected 2 or 10 mins before infusing [1-(14)C]AA in unanesthetized rats. The AA incorporation coefficient k(*) (a marker of the AA signal) was measured in 80 brain regions by quantitative autoradiography. Nicotine, compared to saline, when administrated 2 mins before [1-(14)C]AA infusion, significantly decreased k(*) for AA in 26 regions, including cerebral cortex, thalamus, and habenula-interpeduncular regions, by 13% to 45%. These decreases could be entirely prevented by pretreatment with mecamylamine (1.0 mg/kg, subcutaneously). When administered 10 mins before [1-(14)C]AA infusion, nicotine did not alter any value of k(*). In summary, nicotine given to unanesthetized rats rapidly reduces signaling involving AA in brain regions containing nAChRs, likely by modulating the presynaptic release of neurotransmitters. The effect shows rapid desensitization and is produced at a nicotine dose equivalent to smoking one cigarette in humans.
Chang
Lisa
L
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rapoport
Stanley I
SI
Nguyen
Henry N
HN
Greenstein
Dede
D
Chen
Mei
M
Basselin
Mireille
M
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011978:Receptors, Nicotinic / Q000378:metabolism
D011978:Receptors, Nicotinic; D016718:Arachidonic Acid; D008464:Mecamylamine; D009538:Nicotine; D015232:Dinoprostone