BEHAVIORAL AND ELECTROENCEPHALOGRAPHIC PROPERTIES OF DULOXETINE (LY248686), A REUPTAKE INHIBITOR OF NOREPINEPHRINE AND SEROTONIN, IN MICE AND RATS

Duloxetine is a dual inhibitor of norepinephrine and serotonin reuptak e. Duloxetine (3.13-50 mg/kg p.o.) significantly prevented tetrabenazi ne (1 and 50 mg/kg s.c.)-induced ptosis in mice and rats. Moreover, du loxetine (1.56-12.5 mg/kg p.o.) also inhibited reserpine (1 mg/kg s.c. )-induced hypothermia in mice. When duloxetine (12.5-100 mg/kg p.o.) a nd 5-hydroxytryptophan (80 and 100 mg/kg i.p.), a precursor of seroton in, were administered simultaneously to mice and rats, head movement b ehavior and tremor were observed. In addition, duloxetine (25-100 mg/k g p.o.) significantly attenuated immobility in forced swimming in mice , as equally effective as commonly used antidepressant drugs. Duloxeti ne (12.5-25 mg/kg p.o.) significantly decreased rapid eye movement sle ep and slow-wave deep sleep and increased the awake period, as shown i n the rat EEG. However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a c holinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine- induced tremor in part. These results indicated that duloxetine produc ed behavioral and electroencephalographic responses resulting from the inhibition of norepinephrine and serotonin reuptake in vivo, and that it had a weak anticholinergic action. Therefore, duloxetine may be cl inically useful as an antidepressant.