The effects of a potential antidepressant, 2,4-dimethyl-5-(3-fluorophenyl)-3h-1,2,4-triazole-3-thione, in an electrophysiological model responsive to desipramine

The effects of acute and chronic administration of desipramine (DMI) and the potential antidepressant, MDL 26,479 (2,4-dimethyl-5-(3-fluorophenyl)-3H-1,2,4-triazole-3-thione) were compared on the sensitivity of Purkinje neurons in the cerebellum of the rat to iontophoretically applied norepinephrine (NE) and γ-aminobutyric acid (GABA). Neither compound, administered acutely at 10 mg/kg (i.p.), altered the spontaneous firing rate of Purkinje neurons or the depression of the rate caused by iontophoresed NE. However, MDL 26,479 did significantly reduce the enhancement of inhibitory responses to GABA, produced by NE. Administered chronically (10 mg/kg× 21 days, i.p.), neither compound altered the slowing of Purkinje neurons evoked by NE. Chronic treatment with MDL 26,479, but not with DMI, produced a small but significant decrease in average spontaneous firing rate of Purkinje neurons. Both compounds substantially attenuated the enhancement of the inhibitory responses to GABA produced by NE, with MDL 26,479 having a more marked effect than DMI. These effects of MDL 26,479 on the activity of Purkinje neurons are consistent with the compound having antidepressant potential and further suggest, since similar effects were seen after a single dose, that the compound may have a rapid onset of antidepressant action.