title: Depletion of serotonin, dopamine and noradrenaline in aged rats decreases the therapeutic effect of nicotine, but not of tetrahydroaminoacridine.
abstract: The present study investigates the effects of nicotine (0.1 and 0.3 mg/kg) and tetrahydroaminoacridine (3 mg/kg) treatment on spatial navigation in aged control and p-chlorophenylalanine (a serotonin (5-hydroxytryptamine, 5-HT) synthesis inhibitor, 400 mg/kg on 3 successive days, i.p.)-treated rats. p-Chlorophenylalanine did not aggravate the water maze failure of aged rats. Nicotine (0.3 mg/kg) was more effective than tetrahydroaminoacridine (3 mg/kg) in promoting water maze navigation by aged control rats. p-Chlorophenylalanine blocked the therapeutic effect of nicotine (0.3 mg/kg),but did not decrease the effect of tetrahydroaminoacridine (3 mg/kg) in aged rats. Frontal cortex dopamine levels and choline acetyltransferase activity were lower in aged rats, but 5-HT and noradrenaline levels were unaltered. p-Chlorophenylalanine decreased selectively 5-HT levels in young rats, but in aged rats 5-HT, dopamine and noradrenaline levels were decreased. These results suggest that aged rats are neurochemically more sensitive to p-chlorophenylalanine treatment and that tetrahydroaminoacridine may more effectively than nicotine stimulate spatial learning if 5-HT, dopamine and noradrenaline systems are severely affected.
authors.affiliation: Department of Neurology, University of Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Riekkinen
authors.forename: L
authors.initials: L
authors.lastname: Aroviita
authors.forename: M
authors.initials: M
authors.lastname: Kivipelto
authors.forename: K
authors.initials: K
authors.lastname: Taskila
authors.forename: P
authors.initials: P
authors.lastname: Riekkinen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013619:Tacrine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D012701:Serotonin; D013619:Tacrine; D009538:Nicotine; D010134:Fenclonine; D004298:Dopamine; D009638:Norepinephrine