Ethanol-induced increases in extracellular dopamine are blunted in brain-derived neurotrophic factor heterozygous mice

Bosse, Kelly E.; Mathews, Tiffany A.

doi:10.1016/j.neulet.2010.12.010

Cited by 17 publications

(9 citation statements)

References 36 publications

(63 reference statements)

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“…Neurotrophins can modulate neuroadaptations in addictive behavior and alcohol consumption is influenced by the interaction between BDNF and dopamine (DA) transmission (Bosse & Mathews ). It has been shown that EtOH exposure in sire mice may induce ADHD‐like (attention deficit hyperactivity disorder) effects such as hyperactive, inattentive and impulsive behaviors in the offspring (Kim et al .…”

Section: Discussionmentioning

confidence: 99%

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

et al. 2015

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Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75 NTR , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75 NTR in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

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Section: Discussionmentioning

confidence: 99%

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

et al. 2015

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“…Ethanol-induced modifications of gene expression in reward-associated brain regions are considered to contribute to long-lasting neuroadaptations and behavioral abnormalities (Lewohl et al, 2000;Kerns & Miles, 2008;Piechota et al, 2010). In addition, extensive research has implicated BDNF neurotransmission in the regulation of responses to drug-related behavioral consequences in general (for review, see for example Corominas et al, 2007;Thomas et al, 2008;Dietz et al, 2009;Ghitza et al, 2010) and ethanol in particular (McGough et al, 2004;Davis, 2008;Bosse & Mathews, 2011). How BDNF may contribute to the rewarding properties of alcohol is not yet known, but it has been shown that exposure to ethanol alters BDNF expression in several brain regions.…”

Section: Discussionmentioning

confidence: 99%

Striatal modulation of BDNF expression using microRNA124a‐expressing lentiviral vectors impairs ethanol‐induced conditioned‐place preference and voluntary alcohol consumption

Bahí

Dreyer

2013

Eur J of Neuroscience

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Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward.

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“…Following centrifugation, the supernatant was isolated and stored at −80 °C. BDNF protein was quantified using an ELISA (Promega E max Immunoassay; Madison, WI) according to kit instructions and as detailed in (Bosse & Mathews, 2011; Szapacs et al, 2004). Samples and standards were run in triplicate in Greiner Bio-One High Binding Flat Bottom 96-well microplates.…”

Section: Methodsmentioning

confidence: 99%

Dysregulation of TrkB phosphorylation and proBDNF protein in adenylyl cyclase 1 and 8 knockout mice in a model of fetal alcohol spectrum disorder

Susick

Chrumka

Hool

et al. 2016

Alcohol

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Brain-derived neurotrophic factor (BDNF) mediates neuron growth and is regulated by adenylyl cyclases (ACs). Mice lacking AC1/8 (DKO) have a basal reduction in the dendritic complexity of medium spiny neurons in the caudate putamen and demonstrate increased neurotoxicity in the striatum following acute neonatal ethanol exposure compared to wild type (WT) controls, suggesting a compromise in BDNF regulation under varying conditions. Although neonatal ethanol exposure can negatively impact BDNF expression, little is known about the effect on BDNF receptor activation and its downstream signaling, including Akt activation, an established neuroprotective pathway. Therefore, here we determined the effects of AC1/8 deletion and neonatal ethanol administration on BDNF and proBDNF protein expression, and activation of tropomyosin-related kinase B (TrkB), Akt, ERK1/2, and PLCγ. WT and DKO mice were treated with a single dose of 2.5 g/kg ethanol or saline at postnatal days 5–7 to model late-gestational alcohol exposure. Striatal and cortical tissues were analyzed using a BDNF enzyme-linked immunosorbent assay or immunoblotting for proBDNF, phosphorylated and total TrkB, Akt, ERK1/2, and PLCγ1. Neither postnatal ethanol exposure nor AC1/8 deletion affected total BDNF protein expression at any time point in either region examined. Neonatal ethanol increased the expression of proBDNF protein in the striatum of WT mice 6, 24, and 48 h after exposure, with DKO mice demonstrating a reduction in proBDNF expression 6 h after exposure. Six and 24 h after ethanol administration, phosphorylation of full-length TrkB in the striatum was significantly reduced in WT mice, but was significantly increased in DKO mice only at 24 h. Interestingly, 48 h after ethanol, both WT and DKO mice demonstrated a reduction in phosphorylated full-length TrkB. In addition, Akt and PLCγ1 phosphorylation was also decreased in ethanol-treated DKO mice 48 h after injection. These data demonstrate dysregulation of a potential survival pathway in the AC1/8 knockout mice following early-life ethanol exposure.

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Ethanol-induced increases in extracellular dopamine are blunted in brain-derived neurotrophic factor heterozygous mice

Cited by 17 publications

References 36 publications

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

Striatal modulation of BDNF expression using microRNA124a‐expressing lentiviral vectors impairs ethanol‐induced conditioned‐place preference and voluntary alcohol consumption

Dysregulation of TrkB phosphorylation and proBDNF protein in adenylyl cyclase 1 and 8 knockout mice in a model of fetal alcohol spectrum disorder

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