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

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 β-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 β-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 via β-adrenergic receptors may be essential for both exercise and antidepressant-induced BDNF regulation. 5-HT_1A and 5-HT_2A/C activation, on the other hand, appear to be most important for antidepressant-induced BDNF regulation, but may also participate significantly in exercise-induced regulation in the CA4.