Alcohol and withdrawal: from animal research to clinical issues

Witte, Philippe H. De; Pinto, Emmanuel; Ansseau, M; Verbanck, Paul

doi:10.1016/s0149-7634(03)00030-7

Cited by 173 publications

(123 citation statements)

References 118 publications

(89 reference statements)

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“…Thus, co-occurrence of alcoholism with neuropsychological disorders such as anxiety and/or depression, can introduce therapeutic challenges for treatment of alcoholism. This is most readily manifested in terms of relapse prevention as such mood disorders may significantly facilitate relapse to alcohol use (Glenn and Parsons, 1991;Driessen et al, 2001;De Witte et al, 2003;Saatcioglu et al, 2008). The results of current study, using an animal model, suggest that administration of an antidepressant can counteract anxiety-and depressive-like behavior induced by chronic alcohol administration.…”

Section: Discussionmentioning

confidence: 73%

“…These co-morbid conditions are manifested more in alcoholic women (50%) than men (30%) (U.S. Department of Health and Human Services, 1993;Kessler et al, 1994;Arolt and Driessen, 1996;Schuckit et al, 1997;Berglund and Ojehagen, 1998;Swendsen et al, 1998;Tondo et al, 1999) and are particularly high during and/or following alcohol withdrawal (Behar et al, 1984;Turnbull and Gomberg, 1988). Anxiety and depression are purported to result in an early and increased alcohol relapse risk (Glenn and Parsons, 1991;De Witte et al, 2003). Whereas the relapse rates for alcoholic patients without co-morbid disorders may be about 40%, these rates jump to about 69% or 77% for alcoholics with anxiety or the combination of anxiety and depressive disorders, respectively (Driessen et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

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Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxietylike behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

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“…This hypothesis is supported by evidence claiming that alcohol consumption may lead to adaptive changes within this neurotransmitter system, resulting in a hyper-glutamatergic state and alterations of glutamate receptors (Littleton, 1995;Spanagel and Zieglgänsberger, 1997;Tsai and Coyle, 1998;De Witte et al, 2003). Consistently, inhibition of glutamate neurotransmission leads to a reversal of a number of ethanol actions, modulating its intake, and, as recently described, reducing drug-seeking behavior in animal models of relapse (Siggins et al, 2003;.…”

Section: Introductionmentioning

confidence: 74%

The Effects of Acamprosate and Neramexane on Cue-Induced Reinstatement of Ethanol-Seeking Behavior in Rat

Bachteler

Economidou

Danysz

et al. 2005

Neuropsychopharmacol

107

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This study examines, for the first time, the effects of acamprosate and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist neramexane on ethanol-seeking induced by alcohol-related environmental stimuli in an animal model of relapse. Wistar rats were trained to operantly self-administer ethanol (10% w/v) or water on a fixed-ratio 1 schedule in a 30-min daily session. Ethanol availability was signaled by an olfactory discriminative stimulus of orange extract (S þ ). In addition, each lever press was accompanied by a 5-s illumination of the operant chamber's house light (CS þ ). Water availability was signaled by anise odor (S À ) and 5-s white noise stimulus (CS À ). After completion of the conditioning phase, indicated by stable levels of responding, operant behaviors were extinguished. Prior to reinstatement tests, animals were divided into groups according to either treatment with acamprosate (100, 200 mg/kg given twice), neramexane (1.0, 2.0, 4.0 mg/kg), or vehicle. In vehicle-treated rats, re-exposure to the S þ /CS þ in the absence of further ethanol availability elicited strong recovery of responding. No effect was observed following presentation of water-paired cues (S À /CS À ). Acamprosate dose-dependently attenuated recovery of responding elicited by ethanol-paired cues (S þ /CS þ ), whereas responding under S À /CS À was not modified by drug administration. Treatment with 1.0 and 2.0 mg/kg of neramexane did not significantly modify responding under both S þ /CS þ and S À /CS À conditions. However, a slight reduction of cue-induced reinstatement of alcohol seeking was observed. At the dose of 4.0 mg/kg, neramexane elicited a marked inhibition of responding following presentation of both ethanol-and water-paired cues. In conclusion, acamprosate significantly and selectively reduced alcohol-seeking elicited by environmental stimuli predictive of alcohol availability. Treatment with neramexane that shares part of the pharmacological effects of acamprosate on NMDA receptors, however, resulted in a nonselective reduction of lever responding.

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“…Even minor symptoms are disabling enough to lead the alcohol dependent individual to resume alcohol consumption at the early stages of withdrawal. The severity of alcohol withdrawal syndrome is therefore a major risk factor for early relapse [216].…”

Section: Introductionmentioning

confidence: 99%

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Nagy

Kolok²,

Boros³

et al. 2005

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Long-term alcohol exposure gives rise to development of physical dependence on alcohol in consequence of changes in certain neurotransmitter functions. Accumulating evidence suggests that the glutamatergic neurotransmitter system, especially the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol's action, since ethanol is a potent inhibitor of the NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory "upregulation" of NMDAR mediated functions supposedly contributing to the occurrence of ethanol tolerance, dependence as well as the acute and delayed signs of ethanol withdrawal.Recently, expression of different types of NMDAR subunits was found altered after long-term ethanol exposure. Especially, the expression of the NR2B and certain splice variant forms of the NR1 subunits were increased in primary neuronal cultures treated intermittently with ethanol. Since NMDA ion channels with such an altered subunit composition have increased permeability for calcium ions, increased agonist sensitivity, and relatively slow closing kinetics, the abovementioned alterations may underlie the enhanced NMDAR activation observed after long-term ethanol exposure. In accordance with these changes, the inhibitory potential of NR2B subunit-selective NMDAR antagonists is also increased, demonstrating excellent potency against alcohol withdrawal-induced in vitro cytotoxicity. Although in vivo data are few with these compounds, according to the effectiveness of the classic NMDAR antagonists in attenuation, not only the physical symptoms,but also some affective and motivational components of alcohol withdrawal, novel NR2B subunit selective NMDAR antagonists may offer a preferable alternative in the pharmacotherapy of alcohol dependence.

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Alcohol and withdrawal: from animal research to clinical issues

Cited by 173 publications

References 118 publications

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

The Effects of Acamprosate and Neramexane on Cue-Induced Reinstatement of Ethanol-Seeking Behavior in Rat

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

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