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 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 via beta-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.
Ivy
A S
AS
Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
Rodriguez
F G
FG
Garcia
C
C
Chen
M J
MJ
Russo-Neustadt
A A
AA
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D005082:Physical Exertion / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology / Q000523:psychology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D018674:Adrenergic Antagonists; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010879:Piperazines; D011725:Pyridines; D012333:RNA, Messenger; D012702:Serotonin Antagonists; D014191:Tranylcypromine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007650:Ketanserin; D011433:Propranolol; D009638:Norepinephrine