The devastating genetic disorder Cockayne syndrome (CS) arises from mutations in the CSA and CSB genes. CS is characterized by progressive multisystem degeneration and is classified as a segmental premature-aging syndrome. The CS complementation group B (CSB) protein is at the interface of transcription and DNA repair and is involved in transcription-coupled and global genome-DNA repair, as well as in general transcription. Recent structure-function studies indicate a process-dependent variation in the molecular mechanism employed by CSB and provide a starting ground for a description of the mechanisms and their interplay.

The 5‐hydroxytryptamine (5‐HT4) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5‐HT4 receptor [3H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5‐HT transporter (S)‐[N‐methyl‐3H]citalopram binding. We also determined the regulation of 5‐HT4 receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5‐HT depletion, and compared this with changes in 5‐HT2A receptor [3H]MDL100907 binding. In the Flinders Sensitive Line, the 5‐HT4 receptor and 5‐HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16–47% down‐regulation of 5‐HT4 receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5‐HT depletion increased the 5‐HT4 receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5‐HT2A receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5‐HT depletion. Thus, the 5‐HT4 receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.

Serotonergic neurotransmission is involved in the regulation

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