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Belknap, John K.; Richards, Susan P.; O’Toole, L. A.; Helms, Melinda L.; Phillips, Tamara J.

doi:10.1023/a:1025615409383

Cited by 132 publications

(34 citation statements)

References 26 publications

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“…The realized heritability observed here is similar to that seen in the other published study using selective breeding to alter voluntary alcohol intake in mice with concurrent access to 10% ethanol and water (Belknap et al 1997), although HAP lines drink considerably more than the high line in that short-term selection study. Interestingly, heritability in the present study was over three times that observed using unidirectional selection for high blood alcohol levels in mice following the 2-h, single bottle drinking in the dark (DID) procedure (Crabbe et al 2009).…”

Section: Discussionsupporting

confidence: 87%

“…One genetic approach that is appealing both in terms of simplicity and face validity is to use selective breeding for differences in free-choice alcohol drinking. Beginning in the 1960’s, at least 6 pairs of high and low alcohol drinking rat lines have been developed (Eriksson 1968; Lumeng et al 1977; Mardones and Segovia-Riquelme 1983; Li et al 1993; Colombo 1997; Le et al 2001), as well as at least 2 sets of mouse lines (Belknap et al 1997; Grahame et al 1999). Lines resulting from these selections reliably show profound differences in alcohol intake resulting from fixation of divergent alleles at loci related to alcohol drinking.…”

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confidence: 99%

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Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

et al. 2010

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Selectively breeding lines of mice and rats to differ in alcohol intake has proven useful for defining which traits correlate with high alcohol drinking behavior, as well as for creating animal models of alcoholism. This study reports the derivation of two novel sets of selected lines, High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) replicate 2 and 3 lines. Mice were mass-selected using the same procedure as in the replicate 1 lines: using HS/Ibg as a progenitor, mice were selected for differences in 2-bottle choice intake of 10% alcohol during a 4-week testing period. In addition, another high drinking line, the crossed HAP (cHAP) line was selectively bred from a progenitors that were a cross of replicate 1 (S27) X replicate 2 (S21) HAP lines. All lines were characterized for saccharin intake. Overall, the response to selection of the HAP and LAP replicate 2 and 3 lines was quite similar. As anticipated, following selection, the cHAP line drank more than either parent HAP line (consuming 26.0 g/kg per day of alcohol by S11), suggesting that this method of crossing replicate lines and selecting from that cross captures more alleles than any single selected line, as well as producing a line with exceptionally high voluntary alcohol intake. As expected, saccharin consumption was highly associated with alcohol consumption; data from all 8 lines (HAP 1, 2, and 3, LAP 1, 2, and 3, HS/Ibg, and cHAP) indicated a genetic correlation between 10% alcohol and 0.32% saccharin intake of 0.917. Overall, these findings show the practicality of developing replicate lines divergent in alcohol preference, and validate a novel procedure for generating very high-drinking mouse populations.

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

et al. 2010

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“…Preliminary evidence from recombinant BXD inbred mouse strains exposed to ethanol SIP indicated that adjunctive drinking as a trait was approximately 27–31% heritable, depending on the drinking measure evaluated (Goldowitz et al, 2006). A comparable realized heritability of 32% was reported in a short-term selection study for preference of a 10% ethanol solution in mice (Belknap, Richards, O’Toole, Helms, & Phillips, 1997). …”

Section: Significant Biological and Environmental Factors That Cosupporting

confidence: 75%

Applications of schedule-induced polydipsia in rodents for the study of an excessive ethanol intake phenotype

Ford

2014

Alcohol

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Schedule-induced polydipsia (SIP) is generated by subjecting a highly motivated animal to a sub-optimal rate of food reinforcement while also providing access to a fluid. SIP is one of several adjunctive (or displacement) behaviors that are expressed in an exaggerated form that is deemed ‘excessive’. This feature makes SIP an attractive model for studying an excessive ethanol drinking phenotype in rodents. Multiple experimental variables are crucial for the full manifestation of adjunctive drinking, including the degree of food deprivation, the inter-pellet interval selected, and the size of the food reward offered. Although these variables were extensively studied and optimized for water polydipsia in rats, a similarly customized approach to ethanol SIP and application of the procedure in mice have largely been curtailed in favor of the default variable values historically used for water SIP in rats. Further, ethanol SIP also requires careful consideration of variables such as taste and ethanol concentration. Investigation of the stress axis and neurochemical systems such as dopamine and serotonin in mediating adjunctive drinking stemmed from two leading hypotheses regarding the underlying mechanisms of SIP generation: 1) SIP as a coping strategy to mitigate stress associated with the aversive environmental condition, and 2) SIP as a displacement of reward in a highly motivated animal. Ethanol SIP is a powerful model of excessive intake because it can generate an ethanol-dependent state and sustain frequent and intoxicating levels of blood ethanol with voluntary oral consumption. The required food deprivation and the loss of the excessive drinking phenotype following removal of the generator schedule are the two main limitations of the model. Future utility of ethanol SIP will be enhanced by more fully dissecting the underlying hormonal and neurochemical mechanisms and optimizing experimental variables for ethanol SIP on a per species and strain basis.

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“…The HS-CC was derived from eight mouse strains, including three wild-derived strains; the genetic diversity captured is ∼90% of that available in M. musculus (Roberts et al, 2007). The preference lines were bred using a short-term selective breeding protocol (Belknap et al, 1997; Metten et al, 2014) that minimizes the stochastic fixation of alleles unrelated to the phenotype of interest, here 2-bottle choice ethanol preference. From the perspective of ethanol preference and consumption, the HS-CC are of interest in that ∼25% of the animals show a preference for ethanol; this differs from a <5% preference found in our HS/NPT mice (unpublished observation) that were derived from eight laboratory mouse strains (Hitzemann et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders

et al. 2018

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The high genetic complexity found in heterogeneous stock (HS-CC) mice, together with selective breeding, can be used to detect new pathways and mechanisms associated with ethanol preference and excessive ethanol consumption. We predicted that these pathways would provide new targets for therapeutic manipulation. Previously (Colville et al., 2017), we observed that preference selection strongly affected the accumbens shell (SH) genes associated with synaptic function and in particular genes associated with synaptic tethering. Here we expand our analyses to include substantially larger sample sizes and samples from two additional components of the “addiction circuit,” the central nucleus of the amygdala (CeA) and the prelimbic cortex (PL). At the level of differential expression (DE), the majority of affected genes are region-specific; only in the CeA did the DE genes show a significant enrichment in GO annotation categories, e.g., neuron part. In all three brain regions the differentially variable genes were significantly enriched in a single network module characterized by genes associated with cell-to-cell signaling. The data point to glutamate plasticity as being a key feature of selection for ethanol preference. In this context the expression of Dlg2 which encodes for PSD-93 appears to have a key role. It was also observed that the expression of the clustered protocadherins was strongly associated with preference selection.

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Cited by 132 publications

References 26 publications

Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

Applications of schedule-induced polydipsia in rodents for the study of an excessive ethanol intake phenotype

Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders

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