Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant

Pharmacology, Biochemistry, and Behavior
A S IvyA A Russo-Neustadt

Abstract

Antidepressants and physical exercise have been shown to increase the transcription of hippocampal brain-derived neurotrophic factor (BDNF). Much evidence regarding the initial actions of antidepressant medications as well as exercise leads to the hypothesis that noradrenergic (NE) and/or serotonergic (5-HT) activation is a key element in the BDNF transcriptional elevation common to both interventions. Currently, we used short-term beta-adrenergic, 5-HT(1A), or 5-HT(2A/C) receptor blockade to characterize the influence of NE and 5-HT systems on BDNF transcription during physical exercise and antidepressant treatment. In situ hybridization revealed that beta-adrenergic blockade significantly blunted the BDNF mRNA elevations due to exercise, and also inhibited the modest elevations in the CA3 and dentate gyrus following short-term treatment with tranylcypromine. In contrast, 5-HT(2A/C) blockade only minimally altered exercise-induced BDNF mRNA levels, but inhibited up-regulation of BDNF transcription via tranylcypromine. Finally, 5-HT(1A) blockade did not inhibit exercise-induced BDNF mRNA elevations, but significantly enhanced levels above those achieved with exercise alone in the CA4. These results suggest that NE activation vi...Continue Reading

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