Article

Chronic ethanol consumption in rats produces residual increases in anxiety 4 months after withdrawal

Department of Psychology, Manhattanville College, 2900 Purchase Street, Purchase, NY 10577, USA. <>
Behavioural Brain Research (Impact Factor: 3.39). 04/2008; 188(1):24-31. DOI: 10.1016/j.bbr.2007.10.009
Source: PubMed

ABSTRACT The present study investigated the long-term effects of ethanol consumption in rats. Subjects were maintained on either an ethanol (alcohol) (2.7-6.7%, v/v) or an isocaloric liquid control diet for 26 consecutive days (M=13.7 g/kg/day). Testing for working memory was conducted in a Morris water maze (2 trials/day for 8 days) and commenced after either a short (19 days) or long (120 days) abstinence period. This was followed by assessment of 72 h retention of passive avoidance. Animals were killed either 41 (short abstinence) or 152 days (long abstinence) post-ethanol and their brains stained with cresyl violet. Assessments of dorsal-ventral and medial-lateral cortical vertices were measured in sections derived from eight coronal planes extending +4.20 to -4.16 mm from Bregma. Results indicated that subjects in the ethanol/long abstinence group exhibited increased state anxiety due to their propensity to be thigmotaxtic (i.e., wall-hugging) in the water maze. Unfortunately, such a swim pattern precluded assessment of working memory in our subjects. No evidence of ethanol-induced memory decrements were observed on retention of passive avoidance. There was some evidence that animals in the ethanol/long abstinent group suffered cortical thinning and slight compression of the CA1 layer within the hippocampus, although age might have contributed to the former effect. It was concluded that chronic ethanol consumption increases anxiety even after an extended period of withdrawal and may conspire with age to affect cortical integrity.

0 Followers
 · 
44 Views
  • Source
    • "that lasts weeks to months (Franke, Kittner, Berger, Wirkner, & Schramek, 1997; Savage, Candon, & Hohmann, 2000). This is accomplished either by exposure to successive increases in ethanol concentration added to drinking water or atmosphere (Robles & Sabria, 2008; Zahr et al., 2009), or ethanol paired with an isocaloric liquid diet, which is thought to control for nutritional deficiencies common to other CET models (Santucci, Cortes, Bettica, & Cortes, 2008; Thinschmidt, Walker, & King, 2003). The result of these treatments is selective neural damage and cognitive impairment that persists following a period of abstinence (Farr, Scherrer, Banks, Flood, & Morley, 2005; Tremwel & Hunter, 1994). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.
    Neurobiology of Learning and Memory 11/2011; 96(4):596-608. DOI:10.1016/j.nlm.2011.01.003 · 4.04 Impact Factor
  • Source
    • "Withdrawal from chronic exposure to ethanol has a reported anxiogenic effect in mammals (Kliethermes, 2005; Roberts et al., 2000; Santucci et al., 2008; Valdez et al., 2002). Previously zebrafish chronically exposed to ethanol in a mostly continuous manner have been tested for their shoal preference with ethanol on board during the behavioral testing (Gerlai et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans.
    Behavioural brain research 06/2011; 219(2):234-9. DOI:10.1016/j.bbr.2011.01.019 · 3.39 Impact Factor
  • Source
    • "Ethanol withdrawal has been shown to depend on molecular and cellular adaptations that lead to persistent , long-term plastic changes in transcription, translation, and synaptic morphology (Kalivas, 2003; Koob et al., 1998; Nestler, 2001). In fact, ethanol withdrawal has been postulated to be associated with specific molecular mechanisms and neuroadaptive changes that may lead to an increased and persistent anxiety state (Kliethermes, 2005; Santucci et al., 2008). The immediate early gene c-fos belongs to a class of genes that encode transcription factors that have been implicated in changes in gene expression that underlie neuronal plasticity (Curran and Morgan, 1995). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study investigated whether nitric oxide (NO)-producing neurons localized in brain areas related to anxiety are also activated after ethanol withdrawal. Male Wistar rats were subjected to an oral ethanol self-administration procedure, in which they were offered 6-8% (vol/vol) ethanol solution for a period of 21 days followed by abrupt discontinuation of the treatment. Control animals received control dietary fluid for similar periods of time. Twenty-four or 48 h after ethanol discontinuation, the animals were exposed to the open field for 10 min. Two hours later, their brains were removed and processed for Fos immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry (which is used to detect NO-producing neurons). Decreased exploratory activity was observed in animals subjected to 24-h withdrawal, characterized by a shorter distance traveled in the open field. Additionally, increased Fos expression was detected in brain areas, such as the cingulate and piriform cortices, several hypothalamic nuclei, amygdaloid nuclei, most subdivisions of the periaqueductal gray matter, and dorsal raphe nucleus (DRN). Ethanol withdrawal activated NO-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus, dorsolateral periaqueductal gray matter (DLPAG), and DRN. The results show that ethanol withdrawal activates NO-producing neurons in the PVN, DLPAG, and DRN, which are brain areas implicated in the modulation of emotional, autonomic, and motor expression of anxiety-like behaviors.
    Alcohol (Fayetteville, N.Y.) 12/2010; 45(7):641-52. DOI:10.1016/j.alcohol.2010.11.007 · 2.04 Impact Factor
Show more