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.

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    • "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). "
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    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
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    • "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). "
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    Behavioural brain research 06/2011; 219(2):234-9. DOI:10.1016/j.bbr.2011.01.019 · 3.39 Impact Factor
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    • "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). "
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