Behavioural effects of fluoxetine and tianeptine, two antidepressants withopposite action mechanisms, in rats

The behavioural effects of two antidepressants with opposite molecular mech anisms, tianeptine 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiaz epin-11-yl)amino]heptanoic acid S,S-dioxide, CAS 66981-73-5) 5 mg/kg p.o., a serotonin reuptake enhancer; and fluoxetine (+/-)-N-methyl-3-phenyl-3-[(a lpha,alpha,alpha-trifluoro-p-tolyl)oxy]propylamine, CAS 54910-89-3)5 mg/kg p.o., a serotonin reuptake inhibitor, were compared after single and prolon ged administration (7 and 14 days) once daily). In all experiments the drug effects were noted at the peak activity time: 30 min after tianeptine and 60 min after fluoxetine administration. In the immobility lime test both dr ugs had a shortening effect on immobility time only after prolonged adminis tration or, in single treatment? after joint administration. A different pa ttern was observed in the two compartment test: both antidepressants showed anxiolytic effects after single and prolonged treatment. However, when the drugs were given in joint administration, the anxiolytic effects were enti rely abolished after single as well as prolonged treatment. In reference sp atial memory test (food finding time in the maze) tianeptine had no effect, whereas fluoxetine caused, after single and prolonged treatment, a very ma rked improvement of reference memory Joint administration of both drugs res ulted in worsening the effects on memory in comparison to fluoxetine alone. bur the results were still significantly better vs. control. In the test f or sedative action (in the Activity,Meter AM-1, where the movements of the animals are counted electronically) only after prolonged treatment with tia neptine a diminished locomotor activity could be observed. It is concluded that in the action of the drugs (beside the effect on serot onin uptake) other mechanisms must play an important role. The diminished l ocomotor activity after tianeptine suggests an influence on the dopaminergi c or GABA-Receptor system.