Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics

Serotonin (5-HT) uptake sites were mapped by autoradiographic means with l3H]cyano-imipramine (PH)CN-IMl), the 5-HTia receptor with [3H]8-hydroxy-2-ldi-n-propyl-amino]tetralin ([3H]8-0H-DPAT), and the 5-HT2 receptor with both [H]ketanserin and l12sl]lysergic acid diethylamide ([125I]LSD) in eight mneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix campartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern <J either 5-HT2 or 5-HTia receptors. For the isocortex, a general organizational scheme was observed with the 5-HTiA receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the mbined distributions of the 5-HTia receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was camplementary to the distribution of 5-HTia and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HTia receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HTia receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n "" 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.