Article

Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase A.

Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Neuroscience (Impact Factor: 3.33). 02/2009; 158(4):1406-15. DOI: 10.1016/j.neuroscience.2008.11.036
Source: PubMed

ABSTRACT Previous human postmortem brain tissue research has implicated abnormalities of 5-HT receptor availability in depression and suicide. Although altered abundance of 5-HT 1A, 5-HT 2A, and 5-HT 2C receptors (5-HT(1A), 5-HT(2A), and 5-HT(2C)) has been reported, the causes remain obscure. This study evaluated the availability of these three receptor subtypes in postmortem brain tissue specimens from persons with a history of major depression (MDD) and normal controls and tested the relationships to protein kinases A and C (PKA, PKC). Samples were obtained from postmortem brain tissue (Brodmann area 10) from 20 persons with a history of MDD and 20 matched controls as determined by a retrospective diagnostic evaluation obtained from family members. Levels of 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor were quantitated via Western blot analyses. Basal and stimulated PKA and PKC activity were also determined. The depressed samples showed significantly increased 5-HT(2A) receptor abundance relative to controls, but no differences in 5-HT(1A) or 5-HT(2C) receptors. Basal and cyclic AMP-stimulated PKA activity was also reduced in the depressed sample; PKC activity was not different between groups. 5-HT(2A) receptor availability was significantly inversely correlated with PKC activity in controls, but with PKA activity in the depressed sample. Increased 5-HT(2A) receptor abundance and decreased PKA activity in the depressed sample are consistent with prior reports. The correlation of 5-HT(2A) receptor levels with PKA activity in the depressed group suggests that abnormalities of 5-HT(2A) receptor abundance may depend on receptor uncoupling and heterologous regulation by PKA.

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