DEPLETION OF SEROTONIN, DOPAMINE AND NORADRENALINE IN AGED RATS DECREASES THE THERAPEUTIC EFFECT OF NICOTINE, BUT NOT OF TETRAHYDROAMINOACRIDINE

The present study investigates the effects of nicotine (0.1 and 0.3 mg /kg) and tetrahydroaminoacridine (3 mg/kg) treatment on spatial naviga tion in aged control and p-chlorophenylalanine (a serotonin (5-hydroxy tryptamine, 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 th an tetrahydroaminoacridine (3 mg/kg) in promoting water maze navigatio n by aged control rats. p-Chlorophenylalanine blocked the therapeutic effect of nicotine (0.3 mg/kg), but did not decrease the effect of tet rahydroaminoacridine (3 mg/kg) in aged rats. Frontal cortex dopamine l evels and choline acetyltransferase activity were lower in aged rats, but 5-HT and noradrenaline levels were unaltered, p-Chlorophenylalanin e decreased selectively 5-HT levels in young rats, but in aged rats 5- HT, dopamine and noradrenaline levels were decreased. These results su ggest that aged rats are neurochemically more sensitive to p-chlorophe nylalanine treatment and that tetrahydroaminoacridine may more effecti vely than nicotine stimulate spatial learning if 5-HT, dopamine and no radrenaline systems are severely affected.