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.