Riekkinen_1996_Eur.J.Pharmacol_308_243

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.