title: Chronic nicotine treatment attenuates alpha 7 nicotinic receptor deficits following traumatic brain injury.
abstract: Traumatic brain injury (TBI) often causes a persistent and debilitating impairment of cognitive function. Although the neurochemical basis for TBI-induced cognitive dysfunction is not well characterized, some studies suggest prominent involvement of the CNS cholinergic system. Previous studies from our laboratories have shown that alpha 7* nicotinic cholinergic receptors (nAChrs) are especially vulnerable to the pathophysiological effects of TBI. Hippocampal and cortical alpha-[(125)I]-bungarotoxin (BTX) expression of alpha 7* nAChrs is significantly decreased in many brain regions following TBI and this reduction persists for at least 3 weeks following injury. In the present study we evaluated whether chronic nicotine infusion could attenuate TBI-induced deficits in alpha 7* nAChr expression. Male Sprague-Dawley rats were sham-operated, or subjected to mild or moderate unilateral cortical contusion injury. Immediately following brain injury, osmotic mini-pumps that delivered chronic saline or nicotine (0.125 or 0.25 mg/kg/h) were implanted. The animals were euthanatized and the brains prepared for nAChr quantitative autoradiography, 7 days following surgery. Brain injury caused significant decreases in BTX binding in several regions of the hippocampus. TBI-induced deficits in alpha 7* nAChr density were reversed in four of the six hippocampal brain regions evaluated following chronic nicotine administration. If TBI-induced deficits in alpha 7* nAChr expression play a role in post-injury cognitive impairment, pharmacological treatments which restore nAChr binding to control levels may be therapeutically useful.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Verbois
authors.forename: S W
authors.initials: SW
authors.lastname: Scheff
authors.forename: J R
authors.initials: JR
authors.lastname: Pauly
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017275:Isradipine / Q000493:pharmacokinetics; D008297:Male; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D009538:Nicotine / Q000008:administration & dosage / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000172:deficiency / Q000378:metabolism; D011725:Pyridines / Q000493:pharmacokinetics; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D020033:Protein Isoforms; D011725:Pyridines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; C082748:epibatidine; D017275:Isradipine