In the present study, single-unit extracellular recording was used in male Wistar rats to compare the effects of a single dose (acute treatment) and a 21-day regimen (long-term treatment) with clomipramine (2.5 mg/kg) and fluoxetine (1.0 mg/kg) on the spontaneous firing rate of nucleus accumbens (NAcc) neurons connected with the ventral tegmental area (VTA). A single injection of clomipramine or fluoxetine did not modify the firing rate of NAcc neurons as compared with the control group, whereas a 21-day regimen reduced the firing rate in comparison with a 21-day saline-treated group, specifically for NAcc neurons that were inhibited by VTA electrical stimulation. These results demonstrate that chronic, but not acute, clomipramine or fluoxetine treatment reduces the firing rate of mesoaccumbens neurons, probably by dopaminergic activation, supporting the hypothesis that the NAcc is involved in the actions of at least these antidepressants. However, additional experiments need to be performed in order to delineate the mechanisms by which chronic clomipramine and fluoxetine treatment reduces the firing rate of NAcc neurons in the rat.

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