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: 3.03).
04/2008; 188(1):24-31. DOI: 10.1016/j.bbr.2007.10.009
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.
Available from: Jeff L Weiner
- "Paradoxically, ethanol withdrawal results in increased anxiety, and this anxiety is potentiated by cyclic intoxication and withdrawal (Becker 2012); thus, withdrawal-related anxiogenesis may promote further drinking and contribute to the development of alcohol dependence (Koob 2013). In support of this, animal studies suggest that the anxiety resulting from extended alcohol exposure persists despite cessation of intake (Valdez et al. 2002; Santucci et al. 2008), and long-abstinent alcoholics complain of enduringly increased anxiety (Willinger et al. 2002; Adinoff et al. 2005). In fact, the severity of anxiety during sobriety can be prognostic of relapse to alcohol abuse (Willinger et al. 2002; Sloan et al. 2003), and alcoholics cite anxiety as a major impetus for reversion to drinking (Sinha et al. 2011). "
[Show abstract] [Hide abstract]
ABSTRACT: Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior. Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period. Our results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P < 0.05). Furthermore, this decrease in drinking is accompanied by significant reductions in the expression of anxiety-like behavior (P < 0.05). These findings suggest that chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a reduction in anxiety-like behavior.
Brain and Behavior 07/2014; 4(4). DOI:10.1002/brb3.230 · 2.24 Impact Factor
Available from: Joseph M Hall
- "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 · 3.65 Impact Factor
Available from: Priya Mathur
- "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 · 3.03 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.