Time of Day and Length of Antidepressant Drug Administration Influence Brain-Derived Neurotrophic Factor and TrkB Levels in Rat Brain

ABSTRACT

The expression of brain-derived neurotrophic factor (BDNF) mRNA and protein and its primary receptor, TrkB mRNA shows circadian oscillations in adult rats; however it has been unclear if juvenile rats also display a similar pattern in circadian oscillations. We determined the levels of BDNF and TrkB mRNA and of BDNF protein at four separate time points during a 24 hperiod in the hippocampus and frontal cortex. The expression of BDNF and TrkB undergoes diurnal oscillation in adult and postnatal day 21 rats, but no significant variation is present in postnatal day 13 rats. Antidepressant drug treatment also is known to influence BDNF and TrkB levels. However, the reported effects of antidepressant drug treatment on BDNF and TrkB are highly variable and may be influenced by multiple factors, including detection method, class of antidepressant drug, and length of administration. BDNF mRNA levels were decreased significantly in the hippocampus after acute desipramine (a tricyclic antidepressant) treatment compared to control. BDNF mRNA and protein levels, as well as TrkB mRNA levels, were unchanged in adult rats after subchronic and chronic treatment with either desipramine or escitalopram (a selective serotonin reuptake inhibitor) and treatment consistent with several reports in the literature. This study defines several important factors that must be taken into account when comparing BDNF and TrkB levels both within and among studies.