The selective serotonin reuptake inhibitors (SSRI) exert a wide range of neurochemical and therapeutic activities. To investigate the neural effectors of SSRIs, we measured the regional cerebral metabolic rates for glucose (rCMRglc) in 56 brain regions of Fischer-344 rats 30 min after intraperitoneal injection of 0.4, 4 or 40 mg/kg of fluoxetine or fluvoxamine or after 4 mg/kg of paroxetine or sertraline. Both shared and drug-specific effects were detected. While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula. The topography and the relation to dose of rCMRglc reductions by SSRIs differ from those of other classes of antidepressants, thus suggesting that SSRIs may specifically modulate brain areas involved in the physiological responses to stress.
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