title: Increased binding potential of [(11)C]raclopride during unilateral continuous microinjection of nicotine in rat striatum observed by positron emission tomography.
abstract: Nicotine injections and nicotine skin patches significantly improve attention, memory, and learning in Alzheimer's disease. In animal studies, nicotine improves the performance of various memory-related tasks, an effect that is thought to be mediated by the neuronal dopaminergic system as systemic administration of nicotine decreased [(11)C]raclopride binding in the anesthetized state. Since high doses of systemically administered nicotine are harmful, we administrated it directly into the rat striatum via microdialysis. We then examined the acute effects of continuous central administration of high doses of nicotine on striatal dopamine concentrations by measuring [(11)C]raclopride binding by positron emission tomography. The concentration of dopamine in the dialysates was significantly increased from basal levels when microdialysis with 100 mM nicotine was initiated. However, contrary to expectations, the binding potential (BP) of [(11)C]raclopride in the nicotine-perfused striatum was significantly higher than that in control striatum. Preinjection of mecamylamine (3 mg/kg), a nicotinic antagonist, had no effect on either extracellular dopamine levels or on the BP of [(11)C]raclopride. These findings suggest that the high dose of local nicotine administration induced mecamylamine-insensitive local increases in extracellular dopamine, but might have decreased the total amount of extracellular dopamine in the striatum.
authors.affiliation: Department of Neurology, Nagoya City Rehabilitation and Sports Center, Nagoya 467-8622, Japan. ttajima@nagoya-rehab.or.jp
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tajima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hatano
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Endo
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Miura
authors.forename: Michitaka
authors.initials: M
authors.lastname: Matsubara
authors.forename: Kengo
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007839:Functional Laterality; D008297:Male; D017551:Microdialysis / Q000379:methods; D008845:Microinjections / Q000379:methods; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors