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1,3-Di-o-tolylguanidine (DTG), opipramol (OPI) and sertraline (SER), sigma site ligands, were studied in Wistar rats and Albino Swiss mice, mainly with regard to their interaction with dopamine drugs. DTG and SER (at the highest doses only) decreased the spontaneous locomotor activity. DTG did not change the amphetamine locomotor hyperactivity, while OPI and SER decreased it. The amphetamine stereotypy was slightly increased (prolonged) by all the three drugs. OPI antagonized the locomotor hyperactivity, stereotypy, aggression and climbing, all those being induced by apomorphine; DTG inhibited only the aggression, while SER-the aggression and climbing (the latter was also inhibited by paroxetine, which showed no affinity for sigma sites). DTG and SER (but not paroxetine) were able to increase the locomotor hyperactivity induced by quinpirole. That effect was antagonized by OPI which-when given alone-did not affect the quinpirole hyperlocomotion. The reserpine-induced akinesia was not affected by DTG, OPI or SER; the L-DOPA hyperactivity in reserpinized rats was changed (increased) by DTG only. DTG and SER (also paroxetine and citalopram), but not OPI, increased the cocaine locomotor hyperactivity. All the three sigma ligands given alone did not evoke catalepsy; the haloperidol- and spiperone-induced catalepsy was attenuated by DTG and OPI, but increased by SER. The MK-801-induced hyperactivity was decreased by DTG, but increased by OPI and SER. In the forced swimming test, only DTG slightly reduced the immobility time; the reduction of the immobility time induced by MK-801 was not changed by DTG, but increased by OPI and SER. Only DTG evoked a dose-dependent decrease in the body temperature, which was not changed by rimcazole. The above results indicate that the sigma site ligands studied differ in their pharmacological profile; however, it is still difficult to determine unequivocally whether they show agonistic or antagonistic properties.