Dependence‐Induced Alcohol Drinking by Alcohol‐Preferring (P) Rats and Outbred Wistar Rats

Gilpin, Nicholas W.; Richardson, H. G.; Lumeng, L.; Koob, George F.

doi:10.1111/j.1530-0277.2008.00678.x

Cited by 50 publications

(67 citation statements)

References 31 publications

(29 reference statements)

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“…The finding that post-withdrawal drinking in P rats was much higher than that in Wistar rats also supports the connection between the severity of withdrawal, greater in P rats, and later drinking episodes. Together with the differential timescale for withdrawal manifestations between the two rat types, our results are consistent with other studies showing a later peak in relapse-like drinking in alcohol-dependent P rats compared with Wistar rats in an operant paradigm (Gilpin et al, 2008). It is especially noteworthy that post-withdrawal drinking in ceftriaxonetreated P rats was comparable to basal Wistar rat drinking levels (2-3 g/kg/day).…”

Section: Discussionsupporting

confidence: 91%

“…It is especially noteworthy that post-withdrawal drinking in ceftriaxonetreated P rats was comparable to basal Wistar rat drinking levels (2-3 g/kg/day). In a study by Gilpin et al (2008), even non-dependent P rats maintained alcohol consumption approximately twice that of Wistar rats. Thus, the present findings suggest that ceftriaxone could be beneficial not only to curb alcohol deprivation-induced increases in drinking, but to initiate moderate consumption as well, even in a model of alcohol dependence.…”

Section: Discussionmentioning

confidence: 97%

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Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

Abulseoud

Camsari

Ruby

et al. 2014

Neuropsychopharmacol

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Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a b-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring 412 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/ kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

Abulseoud

Camsari

Ruby

et al. 2014

Neuropsychopharmacol

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“…The reaction is based on the oxidation of alcohol by alcohol oxidase in the presence of molecular oxygen (alcohol+O 2 → acetaldehyde + H 2 O 2 ). The rate of oxygen consumption is directly proportional to the alcohol concentration [24]. Control rats were treated equally except they were exposed to air.…”

Section: Measurement Of Blood Alcohol Levels (Bal)mentioning

confidence: 99%

“…Alcohol withdrawal behavior included observation for tail rigidity [24], body tremors, and wet dog shakes [29]. Additionally, the rats were tested for hyperactivity, muscle rigidity (catatonia) [29], hyperalgesia (excessive sensitivity to pain) [30], and hyperthermia.…”

Section: Measurement Of Blood Alcohol Levels (Bal)mentioning

confidence: 99%

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Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Boules¹,

Stennett²,

Muhktar³

et al. 2013

J Addict Res Ther

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IntroductionNicotine and alcohol addiction are frequently co-morbid problems [1]. The co-dependence of nicotine and alcohol addiction complicates treatment and is often associated with significant morbidity and mortality. Prevalence of smoking in alcoholics is as high as 90% compared to 30% for the general population [2] and alcohol consumption is associated with high nicotine use [3,4]. Co-morbid cigarette smoking and alcoholism has been associated with higher rates of depression in comparison with non-alcoholic smokers [5] and increased cravings for nicotine in comparison with non alcohol dependent smokers [6]. Additionally, smoker alcoholics are more likely to die from smoking related diseases rather than directly from an alcohol related medical condition [7]. Pharmacotherapeutic options for the treatment of alcohol and tobacco co-dependence are limited. Thus, there is a critical need for the development of novel drugs implementing new therapeutic targets.Neurotensin (NT) is a neuropeptide that is closely associated with, and modulates dopamine (DA) [8], acetylcholine (ACh), glutamate, and γ-aminobutyric acid (GABA) neurotransmission, all of which are involved in addiction and reward pathways. Local administration of NT in the prefrontal cortex (PFC) increases extracellular levels of ACh and GABA [9]. Similar data were obtained with the extracranial injection of the NT agonist NT69L [10], a compound that was developed in our laboratory. NT also enhances GABAergic activity in rat hippocampus [11] and reduces glutamatergic neurotransmission in dorsolateral striatum [12]. However, NT must be administered centrally to have an effect because it is easily degraded by peptidases. Our laboratory has developed many NT agonists that can be administered extracranially and mimic the central effects of NT. The most studied of these agonists is NT69L, which binds with equal affinity to the two well-characterized NT receptors, subtype 1 (NTS1) and subtype 2 (NTS2). Our work with NT69L shows that it blocks nicotine-induced sensitization and nicotine self-administration [13][14][15].In addition to its role in animal models for nicotine addiction, the NT system has been strongly implicated in the neurochemical and behavioral effects of alcohol use [16,17]. Chronic administration of NT69L reduces alcohol preference and consumption in mice through modulation of the NTS1 [18]. Biochemically, NT69L normalizes the nicotine-induced changes in DA [19], the neurotransmitter that promotes the motivational process for both nicotine and alcohol, and the alcohol-induced increase in DA and glutamate in the striatum [20]. Additionally, NT modulates other neurotransmitters implicated in alcohol use disorder (AUD). It causes neurochemical changes similar to acamprosate (the calcium salt of acetylhomotaurine), which is one of three FDA-approved drugs to treat AUD. Administration of acamprosate or NT69L increases extracellular concentration of DA in striatum [10,11] and both acamprosate and NT69L modulate glutamate [21,22].Considering the behav...

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Operant Self‐Administration Models for Testing the Neuropharmacological Basis of Ethanol Consumption in Rats

June

Gilpin

2010

CP Neuroscience

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Operant self-administration procedures are used to assess the neural basis of ethanol-seeking behavior under a wide range of experimental conditions. Rats do not spontaneously selfadminister ethanol in pharmacologically meaningful amounts. This unit provides a step-by-step guide for training rats to self-administer quantities of ethanol that produce moderate to high bloodalcohol content. Different protocols are used for rats that are genetically heterogeneous versus rats that are selectively bred for high alcohol preference. Also, these protocols have different sets of advantages and disadvantages, for example, control for caloric intake or taste between two solutions that maintain operant lever-press behavior. Basic self-administration protocols can also be altered to focus on different aspects of the motivational properties of ethanol (for example, those related to dependence). This unit provides multiple protocols for producing alcohol intake in rats that can be pharmacologically probed relative to a variety of control conditions.

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Dependence‐Induced Alcohol Drinking by Alcohol‐Preferring (P) Rats and Outbred Wistar Rats

Cited by 50 publications

References 31 publications

Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Operant Self‐Administration Models for Testing the Neuropharmacological Basis of Ethanol Consumption in Rats

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