Repeated characterization of alcohol withdrawal reactions in rats chronically exposed to an alcohol liquid diet

Meert, Theo; Huysmans, H.

doi:10.1016/0278-5846(94)90110-4

Cited by 15 publications

(7 citation statements)

References 17 publications

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“…Compared with the painful peripheral neuropathy induced by continuous consumption of ethanol (Dina et al, 2000), we found a more rapid development of an alcohol withdrawal-induced mechanical hyperalgesia using a model of binge drinking. Thus, we provide support for animal (Clemmesen & Hemmingsen, 1984;Becker & Hale, 1993) and clinical studies showing increased severity of CNS withdrawal symptoms following repeated withdrawal episodes (Becker & Hale, 1993;Meert & Huysmans, 1994;Becker, 1998;Duka et al, 2004). Our results extend this phenomenon to signs of painful peripheral neuropathy.…”

Section: Discussionsupporting

confidence: 82%

Ethanol withdrawal induces hyperalgesia mediated by PKCε

Dina

Messing

Levine

2006

Eur J of Neuroscience

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Symptoms of ethanol withdrawal include heightened responses to sensory stimuli, as well as tremors and convulsions. We tested the hypothesis that repeated episodes of ethanol intake and withdrawal exacerbate the symptoms of alcohol-induced peripheral neuropathy. In contrast to the hyperalgesia produced when an alcohol (6.5%)-containing diet was fed continuously to male rats which took 4 weeks to develop (Dina et al., 2000), feeding alcohol (6.5%) in repeated cycles of 4 days of alcohol followed by 3 days without alcohol resulted in a withdrawal-induced hyperalgesia that began at the end of one weekly cycle and reached a maximum during the fourth cycle. For ethanol withdrawal to produce hyperalgesia, ethanol consumption needed to be terminated for a period of 2 days. Paradoxically, as the amount of alcohol consumed decreased, the hyperalgesia induced by withdrawal developed more rapidly, being maximal between 1.4 and 1.6% ethanol. These results suggest that continued exposure to ethanol also has a neuroprotective effect. Withdrawal-induced hyperalgesia, similar to the hyperalgesia induced by continuous, chronic alcohol intake, was inhibited reversibly by intrathecal administration of an antisense oligodeoxynucleotide to protein kinase C (PKC)epsilon.

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Section: Discussionsupporting

confidence: 82%

Ethanol withdrawal induces hyperalgesia mediated by PKCε

Dina

Messing

Levine

2006

Eur J of Neuroscience

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“…Many clinical (Ballenger and Post, 1978;Brown et al, 1988;Malcolm et al, 2000a, b) and animal studies (Maier and Pohorecky, 1989;McCown and Breese, 1990;Becker and Hale, 1993;Kokka et al, 1993;Becker et al, 1997Becker et al, , 1998Meert and Huysmans, 1994;Ulrichsen et al, 1998) support the concept that the increased seizure susceptibility following multiple withdrawals from chronic ethanol resembles a kindling process. Based upon the implication that symptoms of withdrawal other than seizure susceptibility also increase over time in alcoholics (Ballenger and Post, 1978), subsequent experiments showed that repeated withdrawals from chronic ethanol diet over three periods of 5 days, with 2 days of withdrawal between cycles, reduced social interaction between 5 and 6 h after ethanol removal from the final ethanol exposure (Overstreet et al, 2002).…”

Section: Introductionmentioning

confidence: 85%

Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

Breese

Knapp

Overstreet

2003

Neuropsychopharmacol

108

195

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Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposure to three restraint stresses alone altered this measure of anxiety. Further, the repeatedly stressed singly withdrawn rats continued to exhibit a reduction in social interaction 16 days later, upon withdrawal from re-exposure to 5 days of chronic ethanol, consistent with a persistent adaptation by the multiple-stress/withdrawal protocol. Weekly administration of corticosterone in place of stress induced no significant change in social interaction upon withdrawal from the single chronic ethanol exposure, indicative that corticoid release is not responsible for the stress-induced reduction in anxiety-like behavior during withdrawal. In the multiple-withdrawal protocol, stress applied during withdrawal from voluntary ethanol drinking by P-rats facilitated ethanol drinking sufficiently, to induce a withdrawal-induced reduction in social interaction. Administration of a CRF-1 receptor antagonist, a benzodiazepine receptor antagonist, or a 5-HT(1A) receptor agonist prior to each stress minimized sensitization of the withdrawal-induced reduction in anxiety-like behavior. Since these pharmacological consequences on the induction of anxiety-like behavior following the stress/withdrawal protocol are like those previously seen when these drug treatments were given prior to multiple withdrawals, evidence is provided that repeated stresses and multiple withdrawals sensitize the withdrawal reduction in social interaction by similar central adaptive mechanisms.

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“…This theory of kindling seizure activity was subsequently supported by several clinical investigations (Booth and Blow 1993;Brown et al 1988;Lechtenberg and Worner 1990, 1991Worner 1996). Work in rats showing that repeated withdrawals from chronic alcohol facilitate inferior collicular kindling afforded critical support for the kindling hypothesis (McCown and Breese 1990), as did other animal studies that demonstrated enhanced seizure susceptibility following repeated withdrawals (Baker and Cannon 1979;Becker and Hale 1993;Becker et al 1997Becker et al , 1998Clemmesen and Hemmingsen 1984;Kokka et al 1993;Maier and Pohorecky 1989;Meert and Huysmans 1994;Ripley et al 2002;Stephens et al 2001;Ulrichsen et al 1995Ulrichsen et al , 1998. This concept of "kindling" of seizure activity following repeated detoxifications has been a major advance, as it provided an appreciation of the necessity of progressive adaptive change preceding withdrawal-induced seizure activity in alcoholics.…”

Section: Concept Of Kindling Seizure Susceptibility With Repeated Witmentioning

confidence: 81%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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Repeated characterization of alcohol withdrawal reactions in rats chronically exposed to an alcohol liquid diet

Cited by 15 publications

References 17 publications

Ethanol withdrawal induces hyperalgesia mediated by PKCε

Ethanol withdrawal induces hyperalgesia mediated by PKCε

Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

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