Less Editing, Less Depression

Abstract

BEHAVIOR A number of recent studies have fueled a sense of optimism that the fuzzy link between genes and behavior might be firmed up and made explicit, an especially challenging task given the likelihood that the contributions of individual genes (and distinct mutations) to behavior might be only a few percent of the total mix of predisposition, motivation, and environment. Biogenic amines are, of course, front and center in any consideration of mood and affect, and genes encoding various aspects of serotonin function in neurons (synthesis, transport, and receptors) have already been targeted as prime candidates for dysfunction in depression. Englander et al. have used a pair of mice strains to examine the interaction of serotonin receptors, stressful situations, and a selective serotonin reuptake inhibitor (SSRI). They report that, in comparison to C57BL/6 mice, BALB/c animals have lower serotonin levels (due to a polymorphism in tryptophan hydroxylase-2) and are generally easier to stress (via a behavioral despair task). Furthermore, the type 2C serotonin receptor in BALB/c mice undergoes less editing of its pre-messenger RNA, and this yields, in compensatory fashion, receptors that are more sensitive to serotonin. Administering the despair task or the SSRI (the antidepressant fluoxetine) bumps up the extent of RNA editing and presumably titrates downward the responsiveness of postsynaptic neurons to released serotonin. The unexpected finding is that this change in editing due to drug or stress is not seen if both are given together, suggesting that the molecular response may be influenced by the state of the subject and blocked by antidepressants. — GJC J. Neurosci. 25 , 648 (2005).