DOSE-DEPENDENT NORADRENERGIC AND SEROTONERGIC PROPERTIES OF VENLAFAXINE IN ANIMAL-MODELS INDICATIVE OF ANTIDEPRESSANT ACTIVITY

The present study was undertaken to investigate the roughly the precli nical psyche pharmacological profile of venlafaxine, testing a wide ra nge of doses in animal models indicative of antidepressant-like effect s. Venlafaxine was found to be active in mouse forced swimming test (a t 8, 16, 32 and 64 mg/kg) and to increase spontaneous locomotor activi ty (at 16, 32 and 64 mg/kg). Venlafaxine antagonised apomorphine-induc ed (16 mg/kg) hypothermia (at 2, 4, 8, 16, 32 and 64 mg/kg). Pretreatm ent with PCPA significantly attenuated the anti-immobility effects of venlafaxine (8 and 16mg/kg; P<0.01) in the mouse forced swimming test. Venlafaxine at a dose of 32 mg/kg remained active, despite PCPA pretr eatment. DSP-4 significantly attenuated the anti-immobility effects of venlafaxine (16 mg/kg; P < 0.05), whereas venlafaxine at 32 mg/kg rem ained active, despite DSP-LF pretreatment. Venlafaxine was active in t he forced swimming test when administered at sub-effective doses in co mbination with (+/-) pindolol (venlafaxine: I and 2 mg/kg), RU 24969 ( venlafaxine: I, 2 and 4 mg/kg), 8-OH-DPAT (venlafaxine: 4 mg/kg), clon idine (venlafaxine: 1, 2 and 4 mg/kg), lithium (venlafaxine: 1, 2, and 4 mg/kg) and quinine (venlafaxine: 1 and 2 mg/kg). Prior administrati on with NAN-190 antagonised the anti-immobility effects of venlafaxine (8, 16 and 32 mg/kg). Interaction studies did not induce changes in l ocomotor activity. The results of the present study indicated that, at low doses, venlafaxine inhibited serotonin reuptake, while at higher doses it inhibited both serotonin and noradrenaline reuptake.