Silent Trace Eliminates Differential Eyeblink Learning in Abstinent Alcoholics

Fortier, Catherine B.; Maksimovskiy, Arkadiy L.; Venne, Jonathan R.; Lafleche, Ginette; McGlinchey, Regina E.

doi:10.3390/ijerph6072007

Cited by 10 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of the present study show that, in contrast to its effects on set-shifting, CIE exposure induced deficits in reversal learning that are similar to that reported for human alcoholics (Fortier et al, 2008; Fortier et al, 2009), primates (Jedema et al, 2010) and rodents (Brown et al, 2007; Obernier et al, 2002; Ripley et al, 2003; Thomas et al, 2004; Wainwright et al, 1990). That is, performance during reversal learning was significantly impaired following short-term abstinence from alcohol exposure, as CIE mice required more trials, made more errors and performed worse relative to simple discrimination (baseline) than controls.…”

Section: Discussionsupporting

confidence: 84%

“…While tasks that measure the ability to shift attention also require the ability to inhibit responses to the incorrect choice, set-shifting tasks do not directly measure reversal learning. Reports of deficits in reversal learning for alcoholics have only measured task performance during short-term alcohol abstinence (Fortier et al, 2008; Fortier et al, 2009). More clinical studies are needed to determine how long deficits in reversal learning persist in abstinent alcoholics.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice.

Badanich

Becker

Woodward

2011

Behavioral Neuroscience

View full text Add to dashboard Cite

In humans, stroke or trauma-induced damage to the orbitofrontal cortex (OFC) or medial prefrontal cortex (mPFC) results in impaired cognitive flexibility. Alcoholics also exhibit similar deficits in cognitive flexibility suggesting that the OFC and mPFC are susceptible to alcohol-induced dysfunction. The present experiments investigated this issue using an attention set-shifting assay in ethanol dependent adult male C57BL/6J mice. Ethanol dependence was induced by exposing mice to repeated cycles of chronic intermittent ethanol (CIE) vapor inhalation. Behavioral testing was conducted 72 hours or 10 days following CIE exposure to determine whether ethanol-induced changes in OFC-dependent (reversal learning) and mPFC-dependent (set-shifting) behaviors are long-lasting. During early ethanol abstinence (72 hrs), CIE mice showed reduced reversal learning performance as compared to controls. Reversal learning deficits were revealed as greater number of trials to criterion, more errors made and a greater difficulty in performing a reversal learning task relative to baseline performance. Furthermore, the magnitude of the impairment was greater during reversal of a simple discrimination rather than reversal of an intradimensional shift. Reversal learning deficits were no longer present when mice were tested 10 days after CIE exposure suggesting that ethanol-induced changes in OFC function can recover. Unexpectedly, performance on the set-shifting task was not impaired during abstinence from ethanol. These data suggest reversal learning, but not attention set-shifting, is transiently disrupted during short-term abstinence from CIE. Given that reversal learning requires an intact OFC, these findings support the idea that the OFC may be vulnerable to the cognitive impairing actions of ethanol.

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice.

Badanich

Becker

Woodward

2011

Behavioral Neuroscience

View full text Add to dashboard Cite

show abstract

“…Previous studies in our laboratory also demonstrate that mice exposed chronically to ethanol show impaired performance on a reversal learning task (Badanich et al, 2011) shown to require the lOFC (Bissonette et al, 2008). These findings are similar to those reported in human alcoholics (Fortier et al, 2008(Fortier et al, , 2009Verdejo-Garcia et al, 2006), suggesting that alcohol-induced changes in OFC function may lead to loss of behavioral flexibility and poor judgment. Despite these intriguing findings, the effects of chronic alcohol exposure on the fundamental electrophysiological properties of OFC neurons are unknown.…”

Section: Introductionsupporting

confidence: 82%

Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

Nimitvilai

López

Mulholland

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the afterhyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals.

show abstract

“…fMRI studies show that patients with alcohol use disorders (AUDs) have greater activation of the OFC when performing OFC-dependent tasks compared to healthy controls, suggesting that prolonged alcohol consumption impairs OFC function, forcing the region to work harder to execute the same task. Outside of the scanner, patients with AUDs also perform poorly on reversal-learning tasks (Fortier et al, 2009; Fortier et al, 2008) in a manner similar to patients with OFC lesions (Hornak et al, 2004; Tsuchida et al, 2010). …”

Section: Introductionmentioning

confidence: 91%

Withdrawal from chronic intermittent alcohol exposure increases dendritic spine density in the lateral orbitofrontal cortex of mice

McGuier

Padula

López

et al. 2015

Alcohol

View full text Add to dashboard Cite

Alcohol use disorders (AUDs) are associated with functional and morphological changes in subfields of the prefrontal cortex. Clinical and preclinical evidence indicates that the orbitofrontal cortex (OFC) is critical for controlling impulsive behaviors, representing the value of a predicted outcome, and reversing learned associations. Individuals with AUDs often demonstrate deficits in OFC-dependent tasks and rodent models of alcohol exposure show that OFC-dependent behaviors are impaired by chronic alcohol exposure. To explore the mechanisms that underlie these impairments, we examined dendritic spine density and morphology, and NMDA-type glutamate receptor expression in the lateral OFC of C57BL/6J mice following chronic intermittent ethanol (CIE) exposure. Western blot analysis demonstrated that NMDA receptors were not altered immediately following CIE exposure or after 7 days of withdrawal. Morphological analysis of basal dendrites of layer II/III pyramidal neurons revealed that dendritic spine density was also not affected immediately after CIE exposure. However, the total density of dendritic spines was significantly increased after a 7 day withdrawal from CIE exposure. The effect of withdrawal on spine density was mediated by an increase in the density of long, thin spines with no change in either stubby or mushroom spines. These data suggest that morphological neuroadaptations in lateral OFC neurons develop during alcohol withdrawal and occur in the absence of changes in the expression of NMDA-type glutamate receptors. The enhanced spine density that follows alcohol withdrawal may contribute to the impairments in OFC-dependent behaviors observed in CIE treated mice.

show abstract

Silent Trace Eliminates Differential Eyeblink Learning in Abstinent Alcoholics

Cited by 10 publications

References 42 publications

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice.

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice.

Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

Withdrawal from chronic intermittent alcohol exposure increases dendritic spine density in the lateral orbitofrontal cortex of mice

Contact Info

Product

Resources

About