Neuroimaging of serotonin uptake sites and antidepressant binding sites in the thalamus of humans and ‘higher’ animals

This review presents the results of in vitro, ex vivo and in vivo studies carried out primarily for identifying serotonin uptake sites and/or antidepressant binding sites in the brain of humans and 'higher' animals, namely nonhuman primates and pigs. Five lines of evidence are considered. First, studies carried out in vitro using synaptosomes or membrane preparations from human, nonhuman primate, and porcine brain have shown that certain thalamic nuclei are major sites of serotonergic neurotransmission in these species. Second, studies carried out in vitro or ex vivo using autoradiography or immunohistochemistry have indicated that the dorsomedial nucleus and some adjacent regions of the thalamus have a particularly high density of binding sites for antidepressant drugs that are selective serotonin reuptake inhibitors (SSRIs). Third, studies carried out in the living brain of nonhuman primates and pigs have found that SSRIs, radiolabeled for use in PET or SPECT, accumulate to a relatively high degree in midline and dorsal nuclei of the thalamus. Fourth, studies carried out using PET or SPECT radioligands in humans have demonstrated that regions in and around the dorsomedial nucleus of the thalamus are principal sites for accumulation of SSRIs. Fifth, studies of behavior of humans suffering from localized tissue damage in the thalamus have reported that symptoms of mania often occur in the patients, in accordance with the notion that an intact thalamus is required for normal regulation of mood. Taken together, the findings are consistent with the hypothesis that serotonergic neurotransmission in the dorsomedial nucleus of the thalamus could be causally involved in the pathophysiology of affective disease as well as in therapeutic actions of SSRIs.