The degree of inhibition of dopaminergic neurons in the ventral tegmental area induced by selective serotonin reuptake inhibitors is a function of the density-power-spectrum of the interspike interval.
Electrophysiological techniques and computational methods were used to study the effect of the selective serotonin reuptake inhibitors fluvoxamine, paroxetine and sertraline on the basal activity of dopamine neurons in the ventral tegmental area. Acute injection of fluvoxamine, paroxetine and sertraline (20-1280 microg/ kg, i.v.) caused a dose-dependent inhibition of some ventral tegmental area DA neurons but it did not affect the basal firing rate of other DA cells. A Fast-Fourier-Transformation based analysis of the basal activity of 32 ventral tegmental area DA neurons showed a positive correlation between the value of a functional operator (psi) equivalent to the density-power-spectrum of the signals and the degree of selective serotonin reuptake inhibitor-induced inhibition of ventral tegmental area DA cells. All ventral tegmental area DA neurons sampled were subdivided into two subclasses: (A) neurons with no changes in their basal firing rate and (B) neurons showing an approximately linear inhibitory effect in response to selective serotonin reuptake inhibitors. The neurons belonging to subclass A showed a more regular behavior of the interspike interval functions corresponding to lower values detected by the functional operator psi, whereas the neurons belonging to subclass B showed a less regular behavior of interspike interval functions corresponding to higher psi values detected by the same functional operator. Fluvoxamine, paroxetine and sertraline also caused a dose-dependent increase of the percentage of spikes occurring in bursts in neurons belonging to subclass A (low values of psi), whereas the mean basal firing rate of these cells was not affected. It is suggested that this difference in density-power-spectrum could reflect the asymmetry of serotonergic input to the ventral tegmental area DA neurons, and the differential effects of selective serotonin reuptake inhibitors on these neurons might depend on the characteristics of their basal firing mode.
Di Mascio
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Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri, Sud, Santa Maria Imbaro (Chieti), Italy.
Esposito
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D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D015057:1-Naphthylamine; D004298:Dopamine; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline