Effects of tetrahydroaminoacridine and nicotine in nucleus basalis and serotonin-lesioned rats.
The present study was designed to investigate the hypothesis that concurrent degeneration of serotonin and acetylcholine cells may decrease the therapeutic effects of cholinergic drugs on cognitive functioning in Alzheimer dementia. Therefore, we compared the effects of pretraining injections of a cholinesterase inhibitor, tetrahydroaminoacridine (1, 3 and 5 mg/kg i.p.), and nicotine (0.03, 0.1 and 0.3 mg/kg i.p.) on spatial navigation (water maze) and passive avoidance in nucleus basalis- and nucleus basalis+p-chlorophenylalanine-lesioned rats. Nicotine (0.1 and 0.3 mg/kg) promoted passive avoidance performance of nucleus basalis-lesioned rats, but nicotine did not improve performance of combined-lesioned rats. Tetrahydroaminoacridine (3 mg/kg) facilitated passive avoidance performance of nucleus basalis- and combined-lesioned rats. However, tetrahydroaminoacridine-treated nucleus basalis+p-chlorophenylalanine-lesioned rats were not performing better than vehicle-treated nucleus basalis-lesioned rats. Spatial navigation of nucleus basalis and nucleus basalis+p-chlorophenylalanine-lesioned rats was slightly impaired during the first training day and tetrahydroaminoacridine 3 mg/kg restored the performance of combined-lesioned rats. Combined-lesioned rats performed as well as the controls during the other training days. The present results suggest that, in Alzheimer's disease, combined degeneration of nucleus basalis cholinergic and brainstem serotonergic cells decreases the therapeutic effect of nicotine, but not that of tetrahydroaminoacridine.
Riekkinen
P
P
Department of Neurology, University of Kuopio, Finland.
Riekkinen
M
M
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D012701:Serotonin; D013619:Tacrine; D009538:Nicotine; D010134:Fenclonine