Bidirectional selection for susceptibility to ethanol withdrawal seizures inMus musculus

Crabbe, John C.; Kosobud, Ann; Young, Emmett R.; Tam, Brenda R.; McSwigan, John D.

doi:10.1007/bf01065448

Cited by 132 publications

(78 citation statements)

References 13 publications

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“…Two genetically independent WSP and WSR lines have been bred from the HS/Ibg eight-way cross of inbred strains (Crabbe et al, 1985). Mice were bred in the veterinary medical unit at the Veterans Affairs Medical Center (Portland, OR), and female mice from the first genetic replicate (i.e., WSP-1 and WSR-1) were available for use in the present experiment.…”

Section: Animalsmentioning

confidence: 99%

Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice

Beckley¹,

Fretwell²,

Tanchuck³

et al. 2008

Neuropharmacology

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SUMMARYThe GABAergic neurosteroid allopregnanolone (ALLO) has been repeatedly shown to have an increased anticonvulsant effect during ethanol withdrawal in rats and in C57BL/6J mice. In contrast, the seizure prone DBA/2J inbred strain and the Withdrawal Seizure-Prone (WSP) selected line exhibited decreased sensitivity to ALLO's anticonvulsant effect during ethanol withdrawal, with no change in sensitivity in the Withdrawal Seizure-Resistant (WSR) line. To date, only male mice have been tested. Thus, the present study examined ALLO sensitivity during ethanol withdrawal in female WSP and WSR mice, since females display less severe physical symptoms of withdrawal and have higher circulating ALLO levels than males. Female WSP and WSR mice were exposed to ethanol vapor or air for 72 hr. During peak ethanol withdrawal, separate groups of mice were injected with vehicle or ALLO (0, 3.2, 10, or 17 mg/kg, ip) prior to the timed tail vein infusion of pentylenetetrazol (PTZ). ALLO injection significantly increased the threshold dose for onset to PTZ-induced convulsions, indicating an anticonvulsant effect, in female WSP and WSR mice. During ethanol withdrawal, sensitivity to ALLO's anticonvulsant effect was slightly increased in female WSR mice but was significantly decreased in female WSP mice. This line difference in sensitivity to ALLO during ethanol withdrawal in female mice was similar to that in the male mice. Notably, all seizure prone genotypes tested to date displayed tolerance to the anticonvulsant effect of ALLO during ethanol withdrawal, suggesting that decreased sensitivity of GABA A receptors to ALLO may contribute to the increased ethanol withdrawal phenotype.

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Section: Animalsmentioning

confidence: 99%

Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice

Beckley¹,

Fretwell²,

Tanchuck³

et al. 2008

Neuropharmacology

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“…The heterogeneous stock of mice used in all experiments was from four independent breeding populations that had been maintained as controls for three selective breeding projects (Crabbe et al 1985(Crabbe et al , 1987aPhillips et al 1990Phillips et al , 1991Shen et al 1995). They were designated CON1, CON2, WSC1 and WSC2, and all originated from the Ibg HS stock (McClearn and Kakihana 1981).…”

Section: Animalsmentioning

confidence: 99%

Duration of sensitization to the locomotor stimulant effects of ethanol in mice

Lessov

Phillips

1998

Psychopharmacology

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Behavioral sensitization to the psychomotor stimulant effects of some drugs can be quite persistent, lasting for weeks to months after cessation of drug exposure. We investigated the duration of sensitization to the locomotor stimulant effects of 2.0 g/kg ethanol (EtOH) and determined whether repeated EtOH administration would lead to alterations in blood EtOH clearance rates. Female mice were injected (IP) daily for up to 10 consecutive days with saline or EtOH. Baseline activity and acute EtOH locomotor responses were evaluated in Omnitech automated activity monitors (10-min test), with horizontal distance traveled as the measure of locomotion. Locomotor activity response to EtOH was reevaluated immediately after the final daily EtOH injection, and at 5-day intervals during which no EtOH was administered. Tail blood samples for determination of blood ethanol concentrations (BECs) were collected from EtOH-treated mice at the end of activity sessions. Sensitization lasted for up to 29 days, and in two of three of the behavioral sensitization studies, repeated EtOH treatment resulted in elevated BECs. There was no significant effect of repeated EtOH exposure on EtOH clearance rate in a study involving no behavioral testing. The demonstration of persistent behavioral sensitization may imply a lasting hypersensitivity of certain neural pathways to EtOH, thus increasing the reinforcing value of EtOH and the probability of relapse to EtOH drinking after abstinence.

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“…Comparisons among rodent strains and more direct selective breeding of new lines have been useful approaches in moving towards understanding the genetics of alcohol abuse (e.g., Kosobud and Crabbe, 1986;Crabbe et al, 1985;1994). During preliminary screening of alcohol withdrawal symptoms, Long-Evans (LE) rats that began chronic alcohol consumption at an early age (25-35 days old) showed more severe withdrawal symptoms than either the more commonly used SD strain or LE rats that began alcohol consumption as adults.…”

Section: Introductionmentioning

confidence: 99%

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Chung

Wang

Wehman

et al. 2008

Pharmacology Biochemistry and Behavior

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To investigate alcohol dependency and the potential role of age of initial alcohol consumption, Long-Evans (LE) rats were fed an ethanol-containing liquid diet starting at postnatal (P) ages (days): P23-27 (juvenile), P35-45 (adolescent) or P65-97 (young adult). Severity of subsequent withdrawal symptoms was dependent on age when consumption began and on duration of alcohol consumption. Frequency of withdrawal seizures was highest for rats starting consumption as juveniles, intermediate for adolescents and lowest for adults. Normalized to body weight, alcohol consumption was significantly higher for adolescent and juvenile rats than for adults. SpragueDawley rats that began alcohol consumption as adolescents (P35) had a level of alcohol consumption identical to that of the adolescent LE rats but showed much lower frequency of withdrawal seizures when tested after 2, 3 and 5 weeks of alcohol consumption. Based on several indicators, the capacity of the juveniles to metabolize ethanol is equal to or exceeds that of adults. Recoveries from a single dose of ethanol (2.5g ethanol/kg body weight) were faster for juvenile LE rats than adults. The rate of decline in blood ethanol concentration was identical for juvenile and adult rats while the corrected ethanol elimination rate was higher for juveniles. The primary isozyme of alcohol dehydrogenase (ADH) in rat liver, ADH-3, had a similar Km and higher activity in liver preparations from juveniles. In conclusion, LE rats beginning alcohol consumption as juveniles or adolescents develop a severe alcohol withdrawal syndrome that may not be attributed entirely to higher levels of consumption and was not explained by any obvious deficiencies in metabolism.

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Bidirectional selection for susceptibility to ethanol withdrawal seizures inMus musculus

Cited by 132 publications

References 13 publications

Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice

Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice

Duration of sensitization to the locomotor stimulant effects of ethanol in mice

Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

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