High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking

Crabbe, John C.; Ozburn, Angela R.; Metten, Pamela; Barkley-Levenson, Amanda M.; Schlumbohm, Jason P.; Spence, Stephanie E.; Hack, Wyatt R.; Huang, Lawrence C.

doi:10.1016/j.pbb.2017.08.002

Cited by 36 publications

(37 citation statements)

References 51 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the “DID” studies, systemic administration of doses of R(+)-baclofen in the 5–10 mg/kg range markedly reduced alcohol intake in C57BL/6J mice ( 18 , 25 ), selectively bred High Alcohol Preferring 1 (HAP1) mice ( 18 ), and High DID (HDID) mice (selectively bred for high alcohol drinking under the DID regimen) ( 26 ). When tested in the SHAC procedure, baclofen (2.5 and 5 mg/kg, i.p.)…”

Section: Baclofen Effect On Alcohol Drinkingmentioning

confidence: 99%

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

Colombo

Gessa

2018

Front. Psychiatry

View full text Add to dashboard Cite

This paper summarizes the several lines of experimental evidence demonstrating the ability of the prototypic GABAB receptor agonist, baclofen, to suppress multiple alcohol-related behaviors in laboratory rodents and non-human primates exposed to validated experimental models of alcohol use disorder (AUD). Specifically, treatment with baclofen has repeatedly been reported to suppress alcohol-induced locomotor stimulation, alcohol drinking (including binge- and relapse-like drinking), operant oral alcohol self-administration, alcohol seeking, and reinstatement of alcohol seeking in rats and mice. Treatment with baclofen also reduced operant oral alcohol self-administration in baboons. Several of these effects appear to be mediated by GABAB receptors located in the ventral tegmental area. The often observed co-occurrence of “desired” pharmacological effects and “unwanted” sedative effects represents the major drawback of the preclinical, anti-alcohol profile of baclofen. Collectively, these data underline the role of the GABAB receptor in the mediation of several alcohol-related behaviors. These data possess remarkable translational value, as most of the above effects of baclofen have ultimately been reproduced in AUD patients.

show abstract

Section: Baclofen Effect On Alcohol Drinkingmentioning

confidence: 99%

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

Colombo

Gessa

2018

Front. Psychiatry

View full text Add to dashboard Cite

show abstract

“…With B6 mice and a dose range of 2-8 mg/kg, previous data have shown that NTX can reduce EtOH binge-like intake using the DID model, although some sex differences have been reported (Kamdar et al, 2007;Tarragón et al, 2012;Zhou et al, 2019;Navarro et al, 2019). It is important to mention, however, that doses of NTX as high as 10 mg/kg have failed to reduce EtOH intake in mice selected for high blood EtOH levels (HDID lines) obtained using the DID model (Crabbe et al, 2017). HDID lines show remarkably high EtOH intakes (Crabbe et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Morales

Rodríguez-Borillo

Font

et al. 2020

Behavioural Pharmacology

View full text Add to dashboard Cite

Chronic alcohol (EtOH) binging has been associated with long-term neural adaptations that lead to the development of addiction. Many of the neurobiological features of EtOH abuse are shared with other forms of binging, like pathological feeding. The drinkingin-the-dark paradigm (DID) has been used extensively to study the neurobiology of EtOH binge-like drinking due to its ability to promote high intakes relevant to human behavior. DID can also generate high consumption of other tastants, but this procedure has not been fully adapted to study forms of binging behavior that are not alcohol-driven. In the present study we used a modified version of DID that uses multiple bottle availability to promote even higher levels of EtOH drinking in male C57BL/6J mice and allows a thorough investigation of tastant preferences. We assessed whether administration of systemic naltrexone (NTX) could reduce binging on EtOH, sucrose, and saccharin separately as well as in combination. Our multiple bottle DID procedure resulted in heightened levels of consumption compared to previously reported data using this task. We found that administration of the opioid receptor antagonist NTX reduced intakes of preferred, highly concentrated EtOH, sucrose, and saccharin. We also report that NTX was able to reduce overall intakes when animals were allowed to self-administer EtOH, sucrose, or saccharin in combination. Our modified DID procedure provides a novel approach to study binging behavior that extends beyond EtOH to other tastants (i.e., sucrose and artificial sweeteners), and has implications for the study of the neuropharmacology of binge drinking.

show abstract

“…Starting with a genetically heterogeneous progenitor stock (HS/NPT), selective breeding was carried out to create 2 unique High Drinking in the Dark (HDID‐1, HDID‐2) mouse lines that represent models of genetic risk for binge‐like drinking (Crabbe et al, ; Crabbe et al, ). HDID and HS/NPT mice have been extensively characterized (Barkley‐Levenson and Crabbe, ; Barkley‐Levenson and Crabbe, ; Barkley‐Levenson and Crabbe, ; Barkley‐Levenson and Crabbe, ; Barkley‐Levenson et al, ; Barkley‐Levenson et al, ; Crabbe et al, ; Crabbe et al, ; Crabbe et al, ; Crabbe et al, ; Crabbe et al, ; Crabbe et al, ; Crabbe et al, ; Ferguson et al, ; Ferguson et al, ; Fritz et al, ; Iancu et al, ; Iancu et al, ; Metten et al, ). Of particular relevance to the current studies are the findings that HDID mice exhibit behavioral impairment after DID (Crabbe et al, ), withdrawal after a single binge‐drinking session (Crabbe et al, ), and do not exhibit altered preference for saccharin or avoidance of quinine solutions (Crabbe et al, ) or alcohol clearance rates (Crabbe et al, ).…”

mentioning

confidence: 99%

“…We have recently focused on attempting to reduce binge‐like drinking pharmacologically in HDID mice. We first tested whether drugs of known clinical relevance could modulate binge‐like EtOH drinking in HDID mice and found that HDID mice were sensitive to the effects of acamprosate and baclofen, but not naltrexone (Crabbe et al, ). These findings suggested that genetic differences between HDID and C57BL/6 mice may result in different responses to therapeutic compounds.…”

mentioning

confidence: 99%

Effects of Pharmacologically Targeting Neuroimmune Pathways on Alcohol Drinking in Mice Selectively Bred to Drink to Intoxication

Ozburn

Metten

Potretzke

et al. 2020

Alcoholism Clin & Exp Res

Self Cite

View full text Add to dashboard Cite

Background: Rodent models of high alcohol drinking offer opportunities to better understand factors for alcohol use disorders (AUD) and test potential treatments. Selective breeding was carried out to create 2 unique High Drinking in the Dark (HDID-1, HDID-2) mouse lines that represent models of genetic risk for binge-like drinking. A number of studies have indicated that neuroimmune genes are important for regulation of alcohol drinking. We tested whether compounds shown to reduce drinking in other models also reduce alcohol intake in these unique genetic lines.Methods: We report tests of gabapentin, tesaglitazar, fenofibrate, caffeic acid phenethyl ester (CAPE), ibrutinib, and rolipram. Although these compounds have different mechanisms of action, they have all been shown to reduce inflammatory responses. We evaluated effects of these compounds on alcohol intake. In order to facilitate comparison with previously published findings for some compounds, we employed similar schedules that were previously used for that compound.Results: Gabapentin increased ethanol (EtOH) binge-like alcohol drinking in female HDID-1 and HS/NPT mice. Tesaglitazar and fenofibrate did not alter 2-bottle choice (2BC) drinking in male HDID-1 or HS/NPT mice. However, tesaglitazar had no effect on DID EtOH intake but reduced blood alcohol levels (BAL), and fenofibrate increased DID intake with no effects on BAL. CAPE had no effect on EtOH intake. Ibrutinib reduced intake in female HDID-1 in initial testing, but did not reduce intake in a second week of testing. Rolipram reduced DID intake and BALs in male and female HDID-1, HDID-2, and HS/NPT mice.Conclusions: A number of compounds shown to reduce EtOH drinking in other models, and genotypes are not effective in HDID mice or their genetically heterogeneous founders, HS/NPT. The most promising compound was the PDE4 inhibitor, rolipram. These results highlight the importance of assessing generalizability when rigorously testing compounds for therapeutic development.

show abstract

High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking

Cited by 36 publications

References 51 publications

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Effects of Pharmacologically Targeting Neuroimmune Pathways on Alcohol Drinking in Mice Selectively Bred to Drink to Intoxication

Contact Info

Product

Resources

About