SELECTIVE SEROTONIN REUPTAKE INHIBITORS REDUCE THE SPONTANEOUS ACTIVITY OF DOPAMINERGIC-NEURONS IN THE VENTRAL TEGMENTAL AREA

Electrophysiological techniques were used to study the effects of paro xetine, sertraline, and fluvoxamine on the basal activity of dopaminer gic neurons in the ventral tegmental area (VTA) of rats. Acute i.v. ad ministrations of paroxetine (20-1280 mu g/kg), sertraline (20-1280 mu g/kg), and fluvoxamine (20-1280 mu g/kg) caused a slight but significa nt reduction in the firing rate of the VTA dopaminergic cells studied. Paroxetine produced a maximal inhibitory effect of 10 +/- 11% at the cumulative dose of 160 mu g/kg. Sertraline induced a dose-related inhi bition of VTA dopaminergic neurons, which reached its maximum (10 +/- 7%) at the cumulative dose of 1280 mu g/kg. The effect of fluvoxamine on the basal firing rate of VTA dopaminergic neurons was more pronounc ed as compared to that of paroxetine and sertraline, in that it produc ed a maximal inhibition of 17 +/- 12% at the cumulative dose of 1280 m u g/kg. Acute i.v. injections of paroxetine (20-1280 mu g/kg), sertral ine (20-1280 mu g/kg), and fluvoxamine (20-5120 mu g/kg) caused a dose -dependent decrease in the basal firing rate of serotonergic neurons i n the dorsal raphe nucleus (DRN), Paroxetine and sertraline stopped th e spontaneous firing of serotonergic neurons at the cumulative dose of 1280 mu g/kg, whereas fluvoxamine reached the same effect only at the cumulative dose of 5120 mu g/kg, Pretreatment with the 5-HT1A recepto r antagonist tertatolol (1 mg/kg, i.v.) reduced the inhibitory effects of paroxetine, fluvoxamine, and sertraline on the basal activity of s erotonergic neurons in the DRN, Administration of tertatolol induced a 15-fold increase in the ED50 for fluvoxamine. The antagonistic effect of tertatolol was much less evident in blocking the inhibitory action exerted by paroxetine and sertraline on the activity of serotonergic neurons, Pretreatment with tertatolol (1 mg/kg, i.v.) potentiated the inhibitory effect of fluvoxamine on the basal activity of VTA dopamine rgic neurons. Tertatolol did not affect the inhibitory action exerted by paroxetine and sertraline on these neurons. It is concluded that in hibition of the basal firing rate of dopaminergic neurons in the VTA i s a common characteristic of selective serotonin reuptake inhibitors ( SSRIs). The effects of SSRIs on VTA dopaminergic cell activity might b e relevant for their therapeutic action and may explain the origin of the reported cases of akathisia, (C) 1998 Elsevier Science Inc.