Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males

Cheng, Chih‐Ya; Hong, Chen‐Jee; Yu, Younger W.‐Y.; Chen, Tai‐Jui; Wu, Hung‐Chi; Tsai, Shih‐Jen

doi:10.1016/j.molbrainres.2005.07.008

Cited by 111 publications

(99 citation statements)

References 24 publications

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“…Complementary site-specific Bdnf deletion and TrkB inhibition with lentiviral vector approaches Although we have previously used the inducible knock-out technique with Cre-expressing lentivirus in several other brain regions (Heldt et al, 2007;Choi et al, 2010), we had not examined the effect of bdnf gene deletion within the amygdala. In these studies, we bilaterally infected the amygdala of homozygous floxed mice with lentivirus expressing Cre recombinase.…”

Section: Resultsmentioning

confidence: 99%

“…What is ostensibly an evolutionary advantage (having one structure that encodes a variety of emotionally disparate events) also potentially represents a risk for developing comorbid pathologies. For instance, in humans, the val66met Bdnf gene variant has been associated with increased risk for substance abuse (Cheng et al, 2005) as well as impaired fear extinction (Frielingsdorf et al, 2010;Lonsdorf et al, 2010;Soliman et al, 2010). This same variant has been shown to affect amygdalar activity during emotional memory formation (van Wingen et al, 2010 and can also confer a risk for developing disorders that are based upon opposite motivations (i.e., addiction and post-traumatic stress disorder).…”

Section: Discussionmentioning

confidence: 99%

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Bdnf Deletion or TrkB Impairment in Amygdala Inhibits Both Appetitive and Aversive Learning

et al. 2014

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Brain-derived neurotrophic factor (BDNF) is known to have an integral role in establishing stable memories after learning events. The neuroplasticity induced by Pavlovian fear conditioning has likewise been shown to rely on interactions between BDNF and its principal receptor, tyrosine kinase receptor B (TrkB), in the amygdala after training. Although the necessity of amygdala bdnf expression and TrkB activation for associative learning within aversive contexts has been explored, it is unclear to what extent this interaction is involved in appetitive learning. It is also unclear whether the noted increases in amygdala BDNF after fear conditioning are due to local gene transcription and translation or anterograde transmission from cortical regions. To address both of these questions, we used two lentiviral approaches in mice, using both fear conditioning and cocaine-conditioned place preference (CPP), during acquisition and extinction. First, we decreased expression of bdnf mRNA in the amygdala of homozygous floxed mice with a Cre-expressing virus. In a second set of studies, we infused a virus that expressed a dominant-negative TrkB isoform into the same region. These approaches significantly impaired consolidation of fear conditioning and cocaine-CPP, as well as extinction of CPP. Together, these data suggest that BDNF-TrkB signaling is critical for amygdala-dependent learning of both appetitive and aversive emotional memories.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bdnf Deletion or TrkB Impairment in Amygdala Inhibits Both Appetitive and Aversive Learning

et al. 2014

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“…Here, we showed that despite elevated levels of BDNF protein, the number of neurons in the hippocampal DG was lower in the sedentary morphine-dependent rats. One possible explanation is that chronic morphine administration may produce the BDNF gene polymorphism (26).…”

Section: Discussionmentioning

confidence: 99%

Enhancing Hippocampal Neuronal Numbers in Morphine-Dependent Rats by Voluntary Exercise Through a Brain-Derived Neurotrophic Factor-Mediated Mechanism

Rashidy-Pour

Fathollahi

Miladi‐Gorji

et al. 2015

Middle East J Rehabil Health

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Background: Exposure to morphine decreases neurogenesis in the hippocampus. Recent studies have shown that voluntary running decreases the severity of anxiety behaviors and cognitive deficits, and increased synaptic plasticity in morphine-dependent rats. Objectives: This study aimed to investigate whether the morphine dependence-induced attenuation of hippocampal neuron number in rats would be reversed by voluntary running through a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Materials and Methods: The rats were received injections of 10 mg/kg of morphine twice a day over ten days of voluntary running. A specific antagonist of BDNF action (TrkB-IgG) was used to block the hippocampal BDNF action during the study period; cytochrome C (Cyt C) was used as the control drug. Results: We found that chronic exposure to morphine had decreased the number of dentate gyrus neurons in sedentary rats receiving Cyt C or IgG in comparison to the control rats (P < 0.05). Moreover, exercise groups receiving saline or morphine showed an increase in the number of neurons following ten days running; blocking the BDNF action with TrkB-IgG fully inhibited this effect (both, P = 0.0001). Conclusions: This study demonstrates that that voluntary exercise can ameliorate the attenuation of hippocampal neuron number induced by morphine dependence through a BDNF-mediated mechanism. Thus, physical activity might have a potential role in ameliorating chronic morphine-induced neuronal changes in the hippocampus.

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“…We investigated the role of BDNF because it has been implicated in the development of synaptic architecture throughout development (i.e., Chan et al, 2006;Bao et al, 1999;Liou et al;1997;Martinez et al, 1998;Wang et al, 1995) and thus has the potential to be affected by drug insults. In addition, in the adult animal, BDNF has been implicated in changes in plasticity associated with drug exposure, escalation, and abuse (reviewed by Bolanos and Nestler, 2005; see also Berglind et al, 2007;Cheng et al, 2005;Tsai et al, 2007). Finally, there is a substantial literature documenting the role of BDNF in maintaining synaptic plasticity and modulating learning and memory in adult rats (i.e., Bekinschtein et al, 2007;Hall et al, 2000;Linnarsson et al, 1997;Ma et al, 1998;Mu et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…BDNF mRNA is translated into a pre-proprotein that is packaged in secretory vesicles before cleavage to the mature, secreted protein (Mowla et al, 2001). The precursor form of BDNF may actually play a different role in the brain than the mature form (Teng et al, 2005), including affecting learning and memory and drug abuse (Cheng et al, 2005;Hariri et al, 2003;Silhol et al, 2007). We also examined changes in BDNF's high affinity receptor, TrkB.…”

Section: Introductionmentioning

confidence: 99%

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

2008

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Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-α-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water-and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 hr after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning.

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Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males

Cited by 111 publications

References 24 publications

Bdnf Deletion or TrkB Impairment in Amygdala Inhibits Both Appetitive and Aversive Learning

Bdnf Deletion or TrkB Impairment in Amygdala Inhibits Both Appetitive and Aversive Learning

Enhancing Hippocampal Neuronal Numbers in Morphine-Dependent Rats by Voluntary Exercise Through a Brain-Derived Neurotrophic Factor-Mediated Mechanism

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

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