Valproate prevents MK801-induced changes in brain-derived neurotrophic factor mRNA in the rat brain

Valproic acid but not d-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans

“…However, the emotional regulatory effect of VPA is not well understood. VPA increases protein levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and amygdala (Jeon et al, 2006;Jornada et al, 2010) and phosphorylated cyclic adenosine 3 0 ,5 0 -monophosphate (cAMP) response element-binding protein (p-CREB) in the amygdala and nucleus accumbens (Casu et al, 2007), which could stabilize emotional dysregulation.…”

Effect of d-cycloserine and valproic acid on the extinction of reinstated fear-conditioned responses and habituation of fear conditioning in healthy humans: a randomized controlled trial

“…DCS interacts with the glycine binding sites of NMDA receptors in the amygdala to facilitate learning since these receptors are critical for both excitatory fear conditioning and extinction (Castellano et al 2001;Newcomer and Krystal 2001). On the other hand, VPA inhibits HDAC (Göttlicher 2004) and increases mRNA and protein levels of BDNF (Jeon et al 2006); these effects, respectively, stimulate hippocampal and/or amygdala neurogenesis and facilitate learning-related synaptic plasticity, including fear-conditioned memory and fear memory extinction (Rattiner et al 2004;Chhatwal et al 2006;Ou and Gean 2006;Yu et al 2009). It is difficult to understand why the combination of two drugs with different pharmacological mechanisms for enhancing the extinction of conditioned fear would not act synergistically.…”

“…In addition, we determined whether valproic acid (VPA) facilitates the extinction of conditioned fear in healthy humans since a few studies have demonstrated a positive effect of VPA on decreasing the freezing via the extinction of fearconditioned memory in rats (Bredy et al 2007;Bredy and Barad 2008). VPA is as an anticonvulsant that also strongly inhibits histone deacetylase (HDAC) (Göttlicher 2004) and increases messenger RNA (mRNA) and protein levels of brain-derived neurotrophic factor (BDNF) in vitro (Jeon et al 2006). Since regulation of histone acetylation and BDNF is critical for learning-related synaptic plasticity, including fear-conditioned memory and fear memory extinction (Rattiner et al 2004;Chhatwal et al 2006;Ou and Gean 2006), accelerating synaptic plasticity could enhance the consolidation of fear memory.…”

Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder

“…Additionally, studies of the effect of chronic treatment (14 days) with the SSRI fluoxetine in rodents have shown facilitation effects on both initial extinction learning and extinction memory recall (Singewald et al, in press;but see Burghart et al, 2012), and one study of 14 day pretreatment with the SSRI escitalopram in healthy humans has shown facilitated initial extinction learning (Bui et al, 2013). Medications such as valproic acid, lithium and SSRIs have actions on synaptic plasticity and long-term potentiation mediated by increasing brain-derived neurotrophic factor signaling (BDNF; Martinowich & Lu, 2008;Jeon et al, 2006;Hashimoto et al, 2002). Increased BDNF release and signaling has been shown to increase consolidation of fear extinction learning in rodents (Ou & Gean, 2006;Chhatwal et al, 2006;Rattiner et al, 2004), and injection of BDNF directly into the infralimbic cortex has been shown to facilitate extinction memory recall (RosasVidal et al, 2014;Peters et al, 2010).…”