STRESS AND ANTIDEPRESSANTS DIFFERENTIALLY REGULATE NEUROTROPHIN-3 MESSENGER-RNA EXPRESSION IN THE LOCUS-COERULEUS

The mechanisms by which stress and antidepressants exert opposite effe cts on the course of clinical depression are not known. However, poten tial candidates might include neurotrophic factors that regulate the d evelopment, plasticity, and survival of neurons. To explore this hypot hesis, we examined the effects of stress and antidepressants on neurot rophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been imp licated in mood disorders, Using iii situ hybridization, we demonstrat e that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC, In contrast, chronic treatment with antidepres sants decreased NT-3 mRNA levels. The effect occurred in response to a ntidepressants that blocked norepinephrine uptake, whereas serotonin-s pecific reuptake inhibitors did not alter NT-3 levels. Electroconvulsi ve seizures also decreased NT-3 expression in the LC as well as the hi ppocampus, Ntrk3 (neurotrophic tyrosine kinase receptor type 3; former ly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments, Becaus e NT-3 is known to be trophic for LC neurons, our results raise the po ssibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potentia l for autocrine mechanisms of action.