Influences of chronic venlafaxine, olanzapine and nicotine on the hippocampal and cortical concentrations of brain-derived neurotrophic factor (BDNF)

Abstract

Brain-derived neurotrophic factor (BDNF) is a key neurotrophic factor in the brain. It plays an important role in the etiopathogenesis and pharmacotherapy of mental disorders, such as depression or schizophrenia. In recent years, studies have shown that cognitive processes, which are impaired in the course of mental disorders, significantly change BDNF levels in the brain. Administered to rats at a dose of 20 mg/kg (b.d. for 5 weeks), venlafaxine (VEN) increases BDNF levels in the hippocampus and cortex, compared to controls. Administered at a dose of 0.5 mg/kg (b.d. for 5 weeks), olanzapine (OLA) significantly increases BDNF levels in both the cortex and the hippocampus. Similarly, nicotine (NIC) administered at a dose of 0.2 mg/kg (b.d. for 5 weeks) increases BDNF concentrations in both the hippocampus and the cortex. Combined administration of NIC with VEN or OLA does not increase BDNF levels in the hippocampus or the cortex. Based on our study, it can be claimed that BDNF mediates behavioral responses only to drugs used individually and participates in the antidepressant and procognitive effects of the study compounds. BDNF also initiates plastic changes and modulation of synaptic activity in rat brains.

Reduced Brain-Derived Neurotrophic Factor Serum Concentrations in Acute Schizophrenic Patients Increase During Antipsychotic Treatment

“…However, our sample was too small (Table 1) to separate the effects in different medication groups but replicated described effects of an olanzapine mediated BDNF increase, 23,24 which has been observed also in the cortex and hippocampus of rats. 25 In another recent study, serum BDNF was strongly and positively correlated with clozapine dose and increased in clozapine users when compared to patients on typical antipsychotics. 26 Brain-derived neurotrophic factor acts downstream on the phosphatidylinositol-3 kinase (PI3K)/Akt pathway, which has been proposed a pathophysiologically relevant cascade in schizophrenia.…”

Genetic deletion of the adenosine A2A receptor prevents nicotine-induced upregulation of α7, but not α4β2* nicotinic acetylcholine receptor binding in the brain

“…Taken together, these studies suggest that mice lacking adenosine A 2A Rs may have deficits in BDNFdependent mechanisms that are specifically involved in nicotine-induced α7 nAChR upregulation. Interestingly, chronic nicotine treatment has been shown to elevate the expression or the levels of BDNF in the cortex, hippocampus and the amygdala (Aydin et al, 2012;Czubak et al, 2009;Kenny et al, 2000). We observed that in the above brain regions nicotine-induced α7 nAChR upregulation was more pronounced in WT vs. A 2A R KO mice, whereas in the ventral tegmental area, where chronic nicotine administration does not affect BDNF levels (Kivinummi et al, 2011), the effects of A 2A R deletion were less evident, thus providing further support to our suggestion.…”

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

“…For example, it has been reported that in addition to increasing prefrontal DA turnover, chronic administration of olanzapine also elevates brain-derived neurotrophic factor (BDNF) levels in PFC (Czubak et al, 2009;Pillai, 2008). BDNF is a key neurotrophic factor in the brain, and has been shown to have an important role in the formation, maturation, and plasticity of glutamatergic and GABAergic synapses and likely functions as a synaptic morphogen (Carvalho et al, 2008;Gottmann et al, 2009).…”