Ethanol‐Induced Memory Impairment in a Discriminative Avoidance Task is State‐Dependent

Sanday, Leandro; Patti, Camilla L.; Zanin, Karina A.; Fernandes-Santos, Luciano; Oliveira, Larissa Costa; Kameda, Sonia R.; Tufik, Sérgio; Frussa‐Filho, Roberto

doi:10.1111/j.1530-0277.2012.01905.x

Cited by 17 publications

(11 citation statements)

References 53 publications

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“…Ethanol intoxication disrupts learning in a number of tasks in both human and rodent models (Knowles and Duka, 2004; Ray et al, 2012; Sanday et al, 2013); however, little is known about the period of withdrawal following initial ethanol intoxication. Ethanol withdrawal can be observed following a single ethanol exposure (known as acute ethanol withdrawal; Buck et al, 1997), and is characterized by aversive physical and mental effects (Wiese et al, 2000; Karadayian et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

Tipps

Raybuck

Buck

et al. 2015

Alcoholism Clin & Exp Res

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Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes.

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Section: Introductionmentioning

confidence: 99%

Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

Tipps

Raybuck

Buck

et al. 2015

Alcoholism Clin & Exp Res

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“…Specifically, chronic exposure of the brain to ethanol is characterised from comparatively early on by erosion of the hippocampal region (Morris et al, 2009;Crews & Nixon, 2009), loss of interneurons (the primary product of neurogenesis (Mandyam, 2013)), AA (White et al, 2004;Sanday et al, 2013) and olfactory deficits (Ditraglia et al, 1991;Collins, Corso & Neafsey, 1996).…”

Section: Given the General Correlation Between Hydrophobicity And Anamentioning

confidence: 99%

A lipid-leakage model for Alzheimer’s Disease

Rudge

2019

Preprint

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This paper describes a potential new explanation for Alzheimer’s disease (AD), referred to here as the lipid-leakage model. It proposes that AD is caused by the influx of lipids following the breakdown of the blood brain barrier (BBB). The model argues that a principle role of the BBB is to protect the brain from external lipid access. When the BBB is damaged, it allows a mass influx of (mainly albumin-bound) free fatty acids (FFAs) and lipid-rich lipoproteins to the brain, which in turn causes neurodegeneration, amyloidosis, tau tangles and other AD characteristics. The model also argues that, whilst β-amyloid causes neurodegeneration, as is widely argued, its principal role in the disease lies in damaging the BBB. It is the external lipids, entering as a consequence, that are the primary drivers of neurodegeneration in AD., especially FFAs, which induce oxidative stress, stimulate microglia-driven neuroinflammation, and inhibit neurogenesis. Simultaneously, the larger, more lipid-laden lipoproteins, characteristic of the external plasma but not the CNS, cause endosomal-lysosomal abnormalities, amyloidosis and the formation of tau tangles, all characteristic of AD. In most cases (certainly in late-onset, noninherited forms of the disease) amyloidosis and tau tangle formation are consequences of this external lipid invasion, and in many ways more symptomatic of the disease than causative. In support of this, it is argued that the pattern of damage caused by the influx of FFAs into the brain is likely to resemble the neurodegeneration seen in alcohol-related brain damage (ARBD), a disease that shows many similarities to AD, including the areas of the brain it affects. The fact that neurodegeneration is far more pronounced in AD than in ARBD most likely results from the greater heterogeneity of the lipid assault in AD compared with ethanol alone. The lipid-leakage model, described here, arguably provides the first cohesive, multi-factorial explanation of AD that best accounts for all currently known major risk factors, and credibly explains all AD-associated pathologies, including those, such as endosomal-lysosomal dysfunction and excessive lipid droplet formation, that have been too readily overlooked by other accounts of this disease.

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“…In addition, previous studies have highlighted the role of cAMP signaling pathway and the augmentation of CREB levels in ethanol tolerance and dependence [17,18]. It should be noted that memory retrieval in ethanol-induced state dependent learning (STD) is possible unless the subject is situated in a state similar to the acquisition phase [19,20].…”

Section: Introductionmentioning

confidence: 98%