Participation of brainstem monoaminergic nuclei in behavioral depression

Abstract

Several lines of research have now suggested the controversial hypothesis that the central noradrenergic system acts to exacerbate depression as opposed to having an antidepressant function. If correct, lesions of this system should increase resistance to depression, which has been partially but weakly supported by previous studies. The present study reexamined this question using two more recent methods to lesion noradrenergic neurons in mice: intraventricular (ivt) administration of either the noradrenergic neurotoxin, DSP4, or of a dopamine-β-hydroxylase-saporin immunotoxin (DBH-SAP ITX) prepared for mice. Both agents given 2 weeks prior were found to significantly increase resistance to depressive behavior in several tests including acute and repeated forced swim, tail suspension and endotoxin-induced anhedonia. Both agents also increased locomotor activity in the open field. Cell counts of brainstem monoaminergic neurons, however, showed that both methods produced only partial lesions of the locus coeruleus and also affected the dorsal raphe or ventral tegmental area. Both the cell damage and the antidepressant and hyperactive effects of ivt DSP4 were prevented by a prior i.p. injection of the NE uptake blocker, reboxetine. The results are seen to be consistent with recent pharmacological experiments showing that noradrenergic and serotonergic systems function to inhibit active behavior. Comparison with previous studies utilizing more complete and selective LC lesions suggest that mouse strain, lesion size or involvement of multiple neuronal systems are critical variables in the behavioral and affective effects of monoaminergic lesions and that antidepressant effects and hyperactivity may be more likely to occur if lesions are partial and/or involve multiple monoaminergic systems

Genetic identification of a population of noradrenergic neurons implicated in attenuation of stress-related responses

“…In addition, results from the LDB and EPM indicate that activation of Hoxb1 -NE neurons results in decreased anxiety-like behavior. These results stand in contrast to our data from activating En1 -LC neurons and previous reports demonstrating that increased activity of LC-NE neurons facilitates passive stress coping responses 42 – 44 and induces anxiety-like behavior. 1 , 18 Together with our observation that multiple stress-related forebrain regions show reduced neuronal activity upon Hoxb1 -NE activation, the behavioral data indicate that this relatively small population of neurons attenuates the response to acute stressors, a role that appears to be very different from that of LC-NE system.…”

Influence of Cognitive Behavioral Therapy on Mood and Quality of Life After Stent Implantation in Young and Middle-Aged Patients With Coronary Heart Disease

“…The pathogenesis of depression and anxiety has not been fully clarified, and both biological and psychological factors might be involved. [26][27][28] However, psychological interventions in young and middle-aged coronary heart In the present study, the combination of CBT and drug treatment was used to maximize the improvement of symptoms and enhance efficacy. In the CBT process, therapists help patients understand that the psychological obstacles come from dysfunction of their own information processing systems.…”

Differential Neuroprotective and Anti-Inflammatory Effects of L-Type Voltage Dependent Calcium Channel and Ryanodine Receptor Antagonists in the Substantia Nigra and Locus Coeruleus

“…Increased mobility, as observed in LPS-infused rats may not be an adaptive strategy as it leads to increased energy expenditure. Increased mobility during the forced swim task and open field task is associated with damage to the LC (Lin et al, 2011); conversely, increased LC activity is related to increased depressive-like behavior (Stone et al, 2011). Overall, the behavioral data presented here demonstrate that chronic LPS infusion induces an agitation-like phenotype that is maladaptive.…”