Addiction Liability of Albino Rats: Breeding for Quantitative Differences in Morphine Drinking

Nichols, John R.; Hsiao, Sigmund

doi:10.1126/science.157.3788.561

Cited by 98 publications

(15 citation statements)

References 5 publications

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“…However, taste factors alone are unlikely to account totally for a difference so extreme that 1 animal will ingest lethal amounts of a substance while another will even come to avoid the substance's normally preferred vehicle. Suggestions have been made concerning possible commonalities in the genetics and biochemistry of alcohol and opiate addictions (Nichols and Hsiao, 1967;Davis and Walsh, 1970;Eriksson and Kiianmaa, 1971;Nichols, 1972), and C57 and DBA mice are well known for their widely different alcohol preferences (Rodgers and McClearn, 1962;Rodgers, 1966;Whitney et al, 1970). The results of ethanol metabolism are different enough across these genotypes so that DBA mice will form a conditioned aversion to the taste of substances associated with ethanol injection while C57 mice will not (Horowitz and Whitney, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…The method of administering the opiate in an adulterated solution has the definite advantage of reducing preliminary time and effort, and the eventual * To whom reprint requests should be sent result is sometimes a quite high level of drug ingestion Khavari et al, 1975). With few exceptions, studies using opiate ingestion have not investigated genetic factors, and the few genetic studies of opiate ingestion (Nichols and Hsiao, 1967;Eriksson and Kiianmaa, 1971) have not employed adulterated solutions. Here we report simple procedures involving no pretreatment by which mice (Mus rnusculus) can be induced to drink large (in some cases, lethal) amounts of morphine sulfate.…”

Section: Genetics -Saccharinmentioning

confidence: 97%

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Morphine ingestion: Genetic control in mice

et al. 1977

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C57BL/6J mice will drink large amounts of, and display a highly positive preference for, morphine sulfate when it is dissolved in an aqueous solution of sodium saccharin. In identical test situations DBA/2J mice will drink very little of, and display a strong avoidance toward, the morphine-saccharin solution. This clear separation between morphine-accepting and morphine-rejecting animals within a single species combined with a quick and simple method of inducing high levels of morphine ingestion could facilitate the discovery of causal factors in opiate addiction.

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Section: Discussionmentioning

confidence: 99%

Section: Genetics -Saccharinmentioning

confidence: 97%

Morphine ingestion: Genetic control in mice

et al. 1977

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“…Selectively breeding laboratory animals based on differential phenotypes has been critical to our understanding of genetic susceptibility to drug abuse (Nichols and Hsial, 1967;George and Goldberg, 1989;George, 1991;Crabbe and Phillips, 1993;McBride and Li, 1998;Nestler, 2000;Crabbe, 2002). According to this method, only the individuals most strongly expressing the phenotype of interest in a population are mated, and following several generations of selective pressure, the frequency of genes underlying the selected phenotype are increased, resulting in diverging lines.…”

Section: Introductionmentioning

confidence: 99%

Selective breeding for differential saccharin intake as an animal model of drug abuse

Carroll

Morgan

Anker

et al. 2008

Behavioural Pharmacology

108

121

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A positive relationship between the consumption of sweetened dietary substances (e.g. saccharin and sucrose) and drug abuse has been reported in both the human and other animal literature. The proposed genetic contribution to this relationship has been based on evidence from behavioral, neurobiological, and linkage studies in heterogeneous and homogeneous animal populations. Initial work in several laboratories indicated that rodents that are selected for high alcohol consumption also display an increased preference for sweets compared with low alcohol-consuming animals. More recently, Sprague-Dawley rats have been selectively bred based on high saccharin (HiS) or low saccharin (LoS) consumption, and these lines represent an ideal opportunity to determine whether a reciprocal genetic relationship exists between the consumption of sweetened substances and self-administration of drugs of abuse. The purpose of this review is to examine a series of studies on the HiS and LoS rats for drug-seeking and drug-taking behavior using laboratory animal models that represent critical phases of drug abuse in humans. The data support the hypothesis that sweet consumption and drug self-administration are closely related and genetically influenced. Other characteristics of HiS and LoS rats are discussed as possible mediators of the genetic differences such as activity, impulsivity, novelty reactivity, stress, and emotionality. The interaction of sweet preference with biological variables related to drug abuse, such as age, sex, and hormonal influences, was considered, as they may be additive vulnerability factors with consumption of sweet substances. In the studies that are discussed, the HiS and LoS lines emerge as ideal addiction-prone and addiction-resistant models, respectively, with vulnerability or resilience factors that will inform prevention and treatment strategies for drug abuse.

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“…Genetic contributions to opiate preference or avoidance in infrahuman species have become active topics of research (Nichols and Hsiao 1967;Eriksson and Kiianmaa 1971;Horowitz 1976;Horowitz et al 1977;Whitney and Horowitz 1978;Lieblich et al 1983). In particular, the discovery of differences in morphine preference between the C57BL and DBA strains of Mus musculus has extended knowledge about consumption and effects of opiates and suggested clues to the etiology of addiction.…”

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confidence: 99%

Contributions of taste factors and gender to opioid preference in C57BL and DBA mice

1988

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C57BL/6J and DBA/2J mouse strains have been characterized as morphine preferrers and avoiders, respectively (Horowitz et al. 1977). Previously, sweetened morphine solutions were presented with a water alternative, primarily with male subjects. Because sweetness may affect the endogenous opioid system and rodents have shown strain and sex differences in taste preferences, this study looked for strain- and gender-related taste preferences that might have affected opiate consumption. Preference for sweetened and unsweetened morphine and etonitazene was compared across gender and strain. In all choice tests, the control was a similar tasting quinine sulphate solution. Under these conditions, C57BL/6J mice continued to show strong preference for morphine. However, DBA/2J mice drank approximately equal amounts of morphine and quinine solutions, rather than avoiding morphine as when water was the alternative. Both strains appeared surprisingly indifferent to the synthetic opioid etonitazene, compared because it is potent at concentrations having barely perceptible bitterness. This raises the possibility of unexpected differences in post-ingestional effects between morphine and etonitazene. Contrary to reports of gender differences in sweet preference in rats, none were found in either strain of mouse. Neither were there any significant sex differences in opiate preference in either strain. C57 mice preferred sweetness more than did DBA mice.

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Addiction Liability of Albino Rats: Breeding for Quantitative Differences in Morphine Drinking

Cited by 98 publications

References 5 publications

Morphine ingestion: Genetic control in mice

Morphine ingestion: Genetic control in mice

Selective breeding for differential saccharin intake as an animal model of drug abuse

Contributions of taste factors and gender to opioid preference in C57BL and DBA mice

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