The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking

Darcq, Emmanuel; Morisot, Nadège; Phamluong, Khanhky; Warnault, Vincent; Jeanblanc, Jérôme; Longo, Frank M.; Massa, Stephen M.; Ron, Dorit

doi:10.1523/jneurosci.4597-14.2016

Cited by 45 publications

(51 citation statements)

References 70 publications

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“…Here, we used inbred alcohol‐preferring iP rats to assess whether alcohol‐seeking behavior can be modulated via epigenetic transmission through the male germline. In this experiment, rats voluntarily consumed relatively high quantities of alcohol, we observed consumption of 1 g/kg/20 min session on average, which is similar to binge drinking patterns seen in humans . Thus, our finding suggests that this level of alcohol use is not sufficient to influence alcohol consumption in offspring.…”

Section: Discussionsupporting

confidence: 69%

“…In this experiment, rats voluntarily consumed relatively high quantities of alcohol, we observed consumption of 1 g/kg/20 min session on average, which is similar to binge drinking patterns seen in humans. 25,26 Thus, our finding suggests that this level of alcohol use is not sufficient to influence alcohol consumption in offspring.…”

Section: Effect Of Paternal Alcohol Exposure On Voluntary Alcohol Cmentioning

confidence: 66%

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Reduced alcohol‐seeking in male offspring of sires exposed to alcohol self‐administration followed by punishment‐imposed abstinence

Campbell

Flanagan

Marchant

et al. 2018

Pharmacology Res & Perspec

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Emerging evidence has demonstrated that paternal alcohol use can modify the behavior of offspring, particularly male offspring. However, preclinical studies to date have not used voluntary self‐administration of alcohol to examine alcohol‐related behaviors in offspring. Here, we tested the hypothesis that paternal alcohol self‐administration followed by punishment‐imposed abstinence alters alcohol consumption and seeking in male offspring. Male inbred alcohol preferring iP rats were trained to self‐administer alcohol in one context followed by punishment‐imposed suppression of alcohol‐seeking in a different context using contingent footshock. Following this, all rats were bred with alcohol naïve female iP rats. F1 offspring were then trained to self‐administer alcohol in an identical operant paradigm as sires. Alcohol intake and self‐administration behaviors of alcohol‐sired offspring were compared to control‐sired offspring whose fathers had not been exposed to the alcohol operant conditioning experience. We found that paternal alcohol self‐administration reduced context‐induced relapse to alcohol‐seeking in male offspring. These findings indicate that voluntary paternal alcohol experience, operant conditioning, and punishment can result in intergenerational changes in offspring behavior, and that this effect may protect against the vulnerability to relapse after alcohol use. We also noted reduced alcohol responding in the punishment‐associated context in alcohol‐sired offspring, suggesting altered perception of punishment sensitivity or the anxiogenic response to footshock. Collectively, these findings provide evidence that paternal alcohol abuse can impact alcohol‐related behaviors in male offspring.

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Section: Discussionsupporting

confidence: 69%

Section: Effect Of Paternal Alcohol Exposure On Voluntary Alcohol Cmentioning

confidence: 66%

Reduced alcohol‐seeking in male offspring of sires exposed to alcohol self‐administration followed by punishment‐imposed abstinence

Campbell

Flanagan

Marchant

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

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“…p75NTR can also prolong cell-surface TrkA-dependent signaling ( Makkerh et al, 2005 ), thereby enhancing TrkA signaling capacity ( Verdi et al, 1994 ; Epa et al, 2004 ). Interestingly, knockdown of p75NTR expression significantly reduced excessive alcohol intake in rats ( Darcq et al, 2016 ), whereas our own findings suggest that increased p75NTR might be involved in suppressing METH-seeking behavior, since the SS rats also show less cue-induced drug seeking ( Torres et al, 2017 ). This statement hints to the possibility that SS rats might have a better ability to learn and establish memory for adverse events through the activation of the NGF signaling cascade.…”

Section: Discussioncontrasting

confidence: 57%

Selective Activation of Striatal NGF-TrkA/p75NTR/MAPK Intracellular Signaling in Rats That Show Suppression of Methamphetamine Intake 30 Days following Drug Abstinence

Torres

Jayanthi

McCoy

et al. 2017

International Journal of Neuropsychopharmacology

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BackgroundThe continuing epidemic of methamphetamine addiction has prompted research aimed at understanding striatal dysfunctions potentially associated with long-term methamphetamine use.MethodsHere, we investigated transcriptional and translational alterations in the expression of neurotrophic factors in the rat striatum at 30 days following methamphetamine self-administration and footshock punishment. Male Sprague–Dawley rats were trained to self-administer methamphetamine (0.1 mg/kg/injection, i.v.) or saline during twenty-two 9-hour sessions. Subsequently, rats were subjected to incremental footshocks for 13 additional methamphetamine self-administration sessions. This paradigm led to the identification of rats with shock-resistant and shock-sensitive phenotypes. Thirty days following the last footshock session, the dorsal striatum was dissected and processed for gene expression and protein analyses.ResultsPCR arrays revealed significant differences in neurotrophins and their receptors between the 2 phenotypes. Brain-derived neurotrophic factor and nerve growth factor protein levels were increased in the dorsal striatum of both shock-resistant and shock-sensitive rats. However, neurotrophic receptor tyrosine kinase 1 phosphorylation and nerve growth factor receptor protein expression were increased only in the shock-sensitive phenotype. Moreover, shock-sensitive rats showed increased abundance of several phosphorylated proteins known to participate in Ras/Raf/MEK/ERK signaling cascade including cRaf, ERK1/2, MSK1, and CREB.ConclusionsThese findings support the notion that animals with distinct phenotypes for methamphetamine intake in the presence of adverse consequences also display differential changes in an intracellular signaling cascade activated by nerve growth factor-TrkA/p75NTR interactions. Thus, the development of pharmacological agents that can activate nerve growth factor-dependent pathways may be a promising therapeutic approach to combat methamphetamine addiction.

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“…The IAE model is usually not used as a model of EtOH dependence because of the relatively low blood EtOH levels that are achieved and low, or lack of, somatic or emotional signs of withdrawal (Cippitelli et al., ; George et al., ). However, some research groups have observed significant withdrawal symptoms (Fu et al., ; Steensland et al., ) and evidence of compulsive‐like drinking (Carnicella et al., ; Darcq et al., ; Depoy et al., ; Hopf and Lesscher, ; Seif et al., ) in the IAE model that may be relevant to AUDs. The present study confirmed the relevance of the IAE model to AUD by demonstrating that a history of moderate but prolonged (5 months) IAE in young adult rats accelerates the escalation of EtOH drinking and produces compulsive‐like drinking when rats maintain blood EtOH levels that are >150 mg/100 ml.…”

Section: Discussionmentioning

confidence: 99%

Intermittent Access to Ethanol Drinking Facilitates the Transition to Excessive Drinking After Chronic Intermittent Ethanol Vapor Exposure

Kimbrough

Kim

Cole

et al. 2017

Alcoholism Clin & Exp Res

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Background Alcohol binge drinking in humans is thought to increase the risk for alcohol use disorder. Unclear is whether drinking patterns (e.g., binge-like or stable drinking) differentially affect the transition to compulsive-like drinking in dependent individuals. We examined whether chronic binge-like drinking facilitates the transition to compulsive-like drinking in rats. Methods Male Wistar rats were given 5 months of intermittent access to ethanol (IAE) or continuous access to ethanol (CAE) in a two-bottle choice paradigm. Then rats were given chronic intermittent ethanol (CIE) vapor exposure. Escalation of ethanol intake and compulsive-like responding for ethanol, using a progressive-ratio schedule of reinforcement and quinine-adulterated ethanol, were measured. Results IAE rats escalated ethanol drinking after 2 weeks of two-bottle choice, whereas CAE rats exhibited stable ethanol drinking for 5 months. After 8 weeks of CIE, both IAE+CIE and CAE+CIE rats escalated their ethanol intake. However, IAE rats escalated their ethanol intake weeks sooner than CAE rats and exhibited greater ethanol intake. No differences in compulsive-like responding were found between IAE+CIE and CAE+CIE rats. However, both IAE+CIE and CAE+CIE rats showed strong compulsive-like responding compared with rats without prior IAE or CAE. Conclusions Chronic ethanol drinking at stable or escalated levels for several months is associated with more compulsive-like responding for ethanol in rats that are exposed to CIE compared with rats without a prior history of ethanol drinking. Moreover, IAE facilitated the transition to compulsive-like responding for ethanol after CIE exposure, reflected by the escalation of ethanol intake. These results suggest that IAE may facilitate the transition to alcohol use disorder. The present study indicates that despite a moderate level of ethanol drinking, the IAE animal model is highly relevant to early stages of alcohol abuse and suggests that it may be associated with neuroadaptations that produce a faster transition to alcohol dependence.

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The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking

Cited by 45 publications

References 70 publications

Reduced alcohol‐seeking in male offspring of sires exposed to alcohol self‐administration followed by punishment‐imposed abstinence

Reduced alcohol‐seeking in male offspring of sires exposed to alcohol self‐administration followed by punishment‐imposed abstinence

Selective Activation of Striatal NGF-TrkA/p75NTR/MAPK Intracellular Signaling in Rats That Show Suppression of Methamphetamine Intake 30 Days following Drug Abstinence

Intermittent Access to Ethanol Drinking Facilitates the Transition to Excessive Drinking After Chronic Intermittent Ethanol Vapor Exposure

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