Brain-Derived neurotrophic factor Val66Met induces female-specific changes in impulsive behaviour and alcohol self-administration in mice

AbstractBrain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) gates alcohol self-administration in rodents. The major source of BDNF in the striatum is the cortex, and we recently found that BDNF-expressing neurons in the ventrolateral orbitofrontal cortex (vlOFC) extend axonal projections to the DLS. We therefore hypothesized that BDNF in the vlOFC to DLS circuit moderates alcohol intake. We show that overexpression of BDNF in the vlOFC, which activates BDNF signaling in the DLS, is sufficient to attenuate voluntary consumption and seeking of 20% alcohol in the home cage using a two-bottle choice paradigm. Overexpressing BDNF in the vlOFC had no effect on the consumption of a sweetened saccharin solution. In addition, BDNF overexpression in the neighboring motor cortex did not alter alcohol intake. Finally, pathway-specific overexpression of BDNF in DLS-projecting vlOFC neurons significantly reduced alcohol intake and preference. Overall, BDNF in the vlOFC, and specifically in a vlOFC-DLS pathway, keeps alcohol drinking in moderation.

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Brain-derived neurotrophic factor mediates the suppression of alcohol self-administration by memantine

Addiction Biology ◽

10.1111/adb.12039 ◽

2013 ◽

Vol 19 (5) ◽

pp. 758-769 ◽

Cited By ~ 20

Author(s):

Jérôme Jeanblanc ◽

Fabien Coune ◽

Béatrice Botia ◽

Mickaël Naassila

Keyword(s):

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Self Administration

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Targeted over-expression of brain-derived neurotrophic factor in the nucleus accumbens increases goal tracking and nicotine locomotor sensitization, but reduces nicotine self-administration in rats

Drug and Alcohol Dependence ◽

10.1016/j.drugalcdep.2016.08.091 ◽

2017 ◽

Vol 171 ◽

pp. e28

Author(s):

Russell W. Brown ◽

Lauren A. Beuttel ◽

Sara A. Dean ◽

Curtis A. Bradley ◽

James Wherry ◽

...

Keyword(s):

Nucleus Accumbens ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Locomotor Sensitization ◽

Self Administration ◽

Over Expression ◽

Goal Tracking

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A natural antisense to brain-derived neurotrophic factor impairs extinction of drug seeking

10.1101/851949 ◽

2019 ◽

Author(s):

Neil A. Youngson ◽

Matthew R. Castino ◽

Angela Stuart ◽

Kelly A. Kershaw ◽

Nathan M. Holmes ◽

...

Keyword(s):

Rna Sequencing ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Male Rats ◽

Infralimbic Cortex ◽

Self Administration ◽

Drug Seeking ◽

Non Coding Rna ◽

Intravenous Nicotine ◽

Long Non Coding Rna

ABSTRACTBACKGROUNDBrain derived neurotrophic factor (BDNF) is critical for the extinction of drug-seeking. Expression of the Bdnf gene is highly regulated via interactions with non-coding RNA, which themselves are altered following drug exposure. Here we investigate whether a novel long non-coding RNA antisense to Bdnf prevents extinction of drug-seeking. METHODS: Strand-specific RNA sequencing identified a novel long non-coding RNA antisense to exon IV of the Bdnf gene in the ventromedial prefrontal cortex of 8 adult male rats. We then assessed asBdnf-IV expression using strand-specific reverse transcription and quantitative polymerase chain reaction following acquisition, extinction or abstinence from intravenous nicotine self-administration (N = 116). A functional role of the asBdnf-IV in extinction of nicotine-seeking was established by infusing gapmer oligonucleotides into the infralimbic cortex prior to extinction and testing for the effect of these infusions on reinstatement and reacquisition of nicotine-seeking (N = 36).RESULTSRNA sequencing identified the presence of a novel long non-coding RNA antisense to exon IV of the Bdnf gene (asBdnf-IV). Expression of asBdnf-IV was elevated following intravenous nicotine self-administration but not experimenter-administered nicotine. Elevated asBdnf-IV persisted across abstinence and to a greater extent following extinction training, suggesting an interaction between abstinence and extinction learning. In support of this, knockdown of the asBdnf-IV across extinction, but not abstinence, significantly attenuated nicotine-primed reinstatement of nicotine-seeking.CONCLUSIONSasBdnf-IV accumulates in the infralimbic cortex across self-administration training, interferes with the inhibitory learning that underpins extinction of drug-seeking, and predisposes animals to drug relapse.

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