Voluntary consumption of morphine in 15 inbred mouse strains

Belknap, John K.; Crabbe, John C.; Riggan, John P.; O’Toole, L. A.

doi:10.1007/bf02244932

Cited by 95 publications

(107 citation statements)

References 17 publications

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“…Since then, a number of laboratories have pursued studies of this mouse model. Confirmation of the strain difference between B6 and D2 mice in oral morphine preference (Belknap, 1990;Belknap et al, 1993) was followed by a quantitative genetic study that mapped a major locus for the trait to chromosome 10 (Berrettini et al, 1994b). This QTL for oral morphine preference, termed Mop2, was confirmed in a follow-up study (Alexander et al, 1996) and support was generated for the concept that it had a broader influence with regard to the pharmacological effects of morphine being involved also in determining morphine-induced analgesia and the density of [ 3 H]naloxone binding sites in the brain (Belknap et al, 1995).…”

Section: Discussionsupporting

confidence: 45%

“…Compared to other inbred strains, C57BL/6 (B6) mice voluntarily drink large quantities of sweetened morphine solutions (Horowitz et al, 1977;Belknap et al, 1993). Oral morphine intake by B6 mice is attenuated following treatment with opioid antagonists (Berrettini et al, 1994a) suggesting that consumption of morphine solutions elicits opioid receptor-mediated phenomena in the brain.…”

Section: Introductionmentioning

confidence: 99%

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Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Ferraro

Golden

Smith

et al. 2004

Neuropsychopharmacol

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C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of opioid selfadministration. We constructed a set of reciprocal congenic strains between B6 and D2 mice in which the proximal portion of chromosome 10 has been introgressed from one strain onto the background of the other. We tested mice from this pair of reciprocal strains together with progenitor B6 and D2 mice in a two-bottle choice drinking paradigm with morphine and quinine. The results showed that introgression of chromosome 10 alleles from the B6 strain onto a D2 genetic background increased voluntary morphine intake four-fold compared to progenitor D2 mice. Preference for morphine was also increased significantly in D2.B6-Mop2 mice compared to progenitor D2 mice. Conversely, introgression of chromosome 10 alleles from the D2 strain onto a B6 genetic background decreased morphine intake by half compared to progenitor B6 mice in B6.D2 -Mop2 mice; however, high morphine preference was maintained in this congenic strain most likely due to strong quinine aversion. When quinine was eliminated from the control bottle, morphine preference in B6.D2-Mop2 mice was decreased significantly relative to B6 and D2.B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on chromosome 10 proximal to D10Mit124 that has a strong influence on the difference in morphine drinking behavior between B6 and D2 mice.

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Section: Discussionsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Ferraro

Golden

Smith

et al. 2004

Neuropsychopharmacol

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“…Human family studies demonstrate that addiction's vulnerability is influenced both by genes and environmental conditions (Uhl, 1999;True et a., 1999;Vanyukov & Tarter, 2000). Similarly, individual vulnerability to drug abuse in animal models depends on both genetic Belknap et al, 1993a, 1993b, Meliska et al, 1995 and environmental risk factors for addiction (Bowling et al, 1993;Bowling & Bardo, 1994;Cabib et al, 2000;de Jong & Kloet, 2004;Nader & Czoty, 2005).…”

Section: Individual Vulnerabilitysupporting

confidence: 42%

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

Alcaro

Huber

Panksepp

2007

Brain Research Reviews

525

294

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The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors, and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here, views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms.A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spread into BG, DA transmission promotes the "release" of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions.In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors.

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“…Given this fact, various animal models of substance abuse and dependence have been developed and are being used to identify genes involved in these disorders. To identify genes involved in substance abuse, we have used a common mouse model in which two mouse strains, C57BL/6J (B6) and DBA/2J (D2), differ in the expression of behaviors related to substances of abuse, including alcohol (Belknap et al, 1993b) and opiates (Belknap et al, 1993a). With respect to opiates, particularly morphine, B6 and D2 mice differ in voluntary intake (either by consumption of morphine-containing liquid or food, or by operant intravenous self administration) (Horowitz et al, 1977;Belknap et al, 1993a;Suzuki et al, 1991;Elmer GI, personal communication), development of tolerance (Frigeni et al, 1981) and dependence (Belknap, 1990;Suzuki et al, 1991), withdrawal symptoms (Suzuki et al, 1991;Kest et al, 2002), analgesia (Belknap et al, 1995), antinociception (Bergeson et al, 2001), Straub tail (Belknap, 1990), hypothermia (Muraki and Kato, 1987), and reward as determined by conditioned place preference (Cunningham et al, 1992;Orsini et al, 2005).…”

Section: Introductionmentioning

confidence: 45%

Fine Mapping of a Major QTL Influencing Morphine Preference in C57BL/6 and DBA/2 Mice Using Congenic Strains

Doyle

Furlong

Schwebel

et al. 2008

Neuropsychopharmacol

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C57BL/6J (B6) and DBA/2J (D2) mice differ in behaviors related to substance abuse, including voluntary morphine consumption and preference in a two-bottle choice paradigm. Two major quantitative trait loci (QTL) for morphine consumption and preference exist between these strains on chromosomes (Chrs.) 6 and 10 when the two-bottle choice involves morphine in saccharin vs quinine in saccharin. Here, we report the refinement of the Chr. 10 QTL in subcongenic strains of D2.B6-Mop2 congenic mice described previously. With these subcongenic mouse strains, we have divided the introgressed region of Chr. 10 containing the QTL gene(s) into two segments, one between the acromere and Stxbp5 (in D2.B6-Mop2-P1 mice) and the other between marker D10Mit211 and marker D10Mit51 (in D2.B6-Mop2-D1 mice). We find that, similar to B6 mice, the D2.B6-Mop2-P1 congenic mice exhibit a strong preference for morphine over quinine, whereas D2.B6-Mop2-D1 congenic mice avoid morphine (similar to D2 mice). We have also created a line of double congenic mice, B6.D2-Mop2.Qui, which contains both Chr. 10 and Chr. 6 QTL. We find that they are intermediate in their morphine preference scores when compared with B6 and D2 animals. Overall, these data suggest that the gene(s) involved in morphine preference in the morphine-quinine two-bottle choice paradigm are contained within the proximal region of Chr. 10 (which harbors Oprm1) between the acromere and Stxbp5, as well as on distal Chr. 6 between marker D6Mit10 and the telomere.

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Voluntary consumption of morphine in 15 inbred mouse strains

Cited by 95 publications

References 17 publications

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

Fine Mapping of a Major QTL Influencing Morphine Preference in C57BL/6 and DBA/2 Mice Using Congenic Strains

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