Serotonin depletion decreases the therapeutic effect of nicotine, but not THA in medial septal-lesioned rats.
The present study compares the effects of systemic pretraining trial injections of a cholinesterase inhibitor, tetrahydroaminoacridine (THA, 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 (WM) and passive avoidance (step-through PA) performance in medial septal (MS)--or MS+p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor)-lesioned rats. MS-lesion impaired WM and PA acquisition, and serotonin depletion significantly aggravated PA failure of MS-lesioned rats. THA (3 mg/kg) and nicotine (0.1 and 0.3 mg/kg) promoted PA and WM navigation of MS-lesioned rats. THA at a dose of 3 mg/kg improved performance of MS+PCPA-lesioned rats in WM and PA tests, but nicotine did not promote test performance of combined-lesioned rats. This result demonstrates that serotoninergic pathology may decrease the therapeutic effect of nicotine.
Department of Neurology, University of Kuopio, Finland.
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Riekkinen
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Sirviö
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Riekkinen
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology*
D012702:Serotonin Antagonists; D012701:Serotonin; D013619:Tacrine; D009538:Nicotine; D010134:Fenclonine