Analysis of variability of mammary tumor incidence in inbred DBA mice.
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C57BL/6 (C57) and DBA/2 (DBA) inbred mice showed different analgesic responses to cholinergic stimulation. The simultaneous administration of muscarinic and serotonergic agonists, oxotremorine and 5-methoxy-NN-dimethyltryptamine (5-MeODMT), lowered the antinociceptive effect of the cholinergic drug in DBA mice, while no effects were detectable in the C57 strain. These results suggest a strain-dependent behavioural effect of the interaction of cholinergic and serotonergic neuronal systems.
Domoic acid (DA) is an environmental neurotoxin to humans. This work examines whether repeated exposure to subsymptomatic or symptomatic nonlethal doses of domoic acid leads to enhanced symptomatic toxicity in ICR outbred and DBA inbred strains of laboratory mice. A multiple independent exposure paradigm was designed in which doses were administered intraperitoneally every other day for 7 days to achieve four separate exposures to domoic acid. We first examined the effect of repeated exposure on serum clearance of domoic acid. Serum domoic acid levels did not differ following a single or repeated exposure. We next examined the effect of repeated exposure on symptomatic toxicity. The mean toxicity scores did not show a significant difference between single and repeated exposures of either subsymptomatic (0.5 mg/kg) or symptomatic sublethal (2.0 mg/kg) doses of domoic acid. We then examined the effects of repeated domoic acid exposure on a second strain of mouse. DBA mice were chosen based upon their sensitivity to kainic acid-induced seizures; however, the ICR mice were more sensitive to low-dose domoic acid toxicity, particularly in terms of onset and duration of stereotypic scratching behavior. Our results indicate that both strains of mice have comparable concentration-dependent toxic responses to domoic acid; however, differences exist in the magnitude of the response and in specific symptoms. The mean toxicity scores did not show a significant difference when a single exposure (1.0 and 2.0 mg/kg domoic acid) and repeated exposure of the same dose were compared in the DBA mice. This study provides no evidence that short-term repeated exposure to domoic acid in laboratory mice alters domoic acid clearance from the serum, or leads to a more sensitive or a greater neurotoxic response.
Male house mice from two inbred strains, DBA/2 and BA, and their F1 and F2 crosses and backcrosses, B1 and B2, were tested for black-white discrimination learning and 24-hr response retention in a water maze. The BA strain exhibited an inferior learning performance. Nonparametric and biometrical genetic analyses provided only weak evidence of unifactorial inheritance of acquisitions, but somewhat stronger evidence in the case of retention.
Male C57BL/6N (C57) and DBA/2N (DBA) inbred mice were found to differ in open-field behavior after an acute ip injection of ethanol and in the development of tolerance to repeated injections. DBA mice showed only increased activity for 28 min after ethanol doses up to 2.67% g/kg when compared with saline-injected controls. Under the same conditions, C57 mice showed dose-related increases in activity during the first 4 min, followed by dose-related decreases in activity. The effects endured for at least 60 min after injection in both strains. In a third experiment, mice were injected daily with saline or 2.0 g/kg ethanol and tested on Days 1, 5, 9, and 13 for open-field activity. On the 17th day, all mice were tested after an ethanol injection. Neither strain showed tolerance to the activity-stimulating effect of ethanol. Some evidence for tolerance to the effect of ethanol to reduce activity in C57 mice was found. In a fourth experiment, twice-daily injections of ethanol for 10 days produced marked tolerance to the depressant effect of an injection on the 11th day in C57 mice, compared with those in a control group given ethanol for the first time on the 11th day. No tolerance to the stimulant effect of ethanol was seen in C57s. DBA mice were injected twice daily for 19 days but did not display tolerance when tested on Day 10 or on Day 20, Indeed, DBA mice chronically treated with ethanol exhibited more marked stimulation of activity after ethanol than mice treated chronically with saline. Differences in blood ethanol concentrations between the strains could not account for any of the observed differences. Implications for the genetic control of responses to ethanol are discussed.
The effects of post-trial naloxone administration were studied in two inbred strains of mice. C57BL/6 (C57) and DBA/2 (DBA), tested in two different experimental conditions. These were a Y-water maze (requiring escape from water) and the Yerkes--Thompson--Bovet-Nitti apparatus for pattern discrimination (requiring escape from electric shock). Two series of experiments were carried out. In the first series, naloxone improved acquisition in DBA and impaired acquisition in C57 mice either trained to swim towards tha dark or to discriminate between oblique bars. Light-oriented behavior, perhaps due to non-conditioned tendencies, was improved in the Y-water maze following naloxone administration on both strains.
C57BL/6 (C57) and DBA/2 (DBA) inbred mice with posterior parietal cortex or sham lesions were tested in a radial eight-arm maze task with all the paths baited. In the high learner C57 strain, parietal lesions produced a limited impairment of performance without affecting maze-running strategies while the same lesions were found to affect more severely performance in the poor learner DBA strain. Because (1) the processing of spatial information has been found to depend on the conjunctive participation of the hippocampus and the posterior parietal cortex, and (2) DBA mice represent a genetic model of hippocampal dysfunction, the fact that parietal lesions impair spatial performance more severely in the DBA strain suggests that the contribution of the posterior parietal cortex to spatial learning depends on the degree of functionality of the hippocampus.
In this study, the authors explored potential strain and sex differences in nonspatial cognitive ability. Beginning around 90 days of age, male and female C57BL/6J (C57) and DBA/2J (DBA) inbred mice (Mus musculus) were tested on a task of simple odor discrimination learning with 3 repeated reversals. Males learned the task more readily than females, and DBA mice learned the task more readily than C57 mice. All differences became evident after repeated testing. Similarity of perseveration measures indicated the differences were not due to inhibitory deficits. Instead, a phase analysis localized differences to a transitional period of reversal learning. Females increased transitional errors that more likely indicated adaptive sampling strategies than memory failures. C57 females used this strategy indiscriminately, but DBA females sampled as a function of environmental uncertainty.
Possible differences in functionality between the dorsal and the ventral regions of the hippocampus have been investigated in C57BL/6 (C57) and DBA/2 (DBA) inbred mice differing in their hippocampal anatomy. Mice from these two strains with large ventral, small ventral, small dorsal, or sham hippocampal lesions were tested in a visual discrimination radial maze task. Results first showed no strain difference in baseline performance. Examination of the lesion effects in the former strain (C57) revealed that the three lesions produced equivalent performance impairements. In the latter (DBA), ventral lesions, regardless of the size, were found to have a more deleterious effect than had the dorsal lesion. Thus, in C57 mice, the two regions were found to exert a similar control on performance, whereas in DBA mice, there was a modest involvement of the dorsal region associated with an extensive participation of the ventral region. The fact that. in DBA mice, the ventral area appears to be extensively involved when the dorsal hippocampus is poorly functioning suggests the existence of possible compensatory mechanisms between region-related specific operations and, consequently, some form of functional plasticity within the hippocampal formation.
Frequencies of mitogen-reactive B cells have been determined in vitro under culture conditions which allow every growth-inducible B cell to grow and mature into a clone of Ig-secreting PFC. The frequencies of LPS-reactive B cells in the spleen of 6- to 8-wk old mice were between 1 in 3 and 1 in 10 splenic B cells from the following inbred strains of mice: C3H/Tif; BALB/c; BALB/c nu/nu; C57BL/6J; DBA/2J; C57BL/6J x DBA/(2J)F(1); and CBA and A/J. Very similar frequencies are found for lipoprotein-reactive B cells in BALB/c, BALB/c nu/nu, C3H/Tif, and C3H/HeJ mice. No LPS-reactive cells but normal frequencies of lipoprotein-reactive cells were found in C3H/HeJ mice, genetically nonreactive to LPS. SJL mice had significantly lower frequencies of LPS- and of lipoprotein-reactive B cells (1 in approximately 30 B cells). The number of LPS- and of lipoprotein-reactive B cells in spleen was dependent upon the age of the mouse. Newborn spleen contained approximately 10 percent of the number of reactive cells found at 6- to 8-wk of age. From there the frequencies declined again to drop below 5 percent of the maximal number at ages beyond 11 mo. LPS-reactive B cells yielding IgM- and IgG-PFC responses could be found in mesenteric lymph nodes, bone marrow, thymus, thoracic duct, and peripheral blood of 6- to 8-wk old mice. Their frequencies were one in three to five lymph node cells, 1 in 50 to 100 bone marrow cells, one in 10(5) thymus cells, and 1 in 20 to 40 thoracic duct or peripheral blood cells.
The role of the nucleus accumbens (NA) in forming spatial representations was investigated in C57BL/6 (C57) and DBA/2 (DBA) inbred mice. One week before testing, bilateral excitotoxic lesions were performed in the NA using ibotenic acid. Testing consisted of placing mice in an arena containing 5 objects at a fixed location and, after habituation to the object configuration, examining their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects. C57 mice reacted to spatial novelty and DBA mice did not. Both strains, however, reacted to object novelty. The lesion had no effect on C57 mice's performance, but in the DBA mice, it promoted a clear reaction to spatial novelty that was absent in control animals. Radial maze performance also was improved in DBA with NA lesions. Results suggest the NA as a possible site for modulating spatially mediated behaviors in poor-performing subjects.
In this work, we employed three Ah nonresponsive strains of mice, AKR, DBA and DDD, and three Ah responsive ones, C57, BALB and C3H, and prepared hepatic microsomes after the treatment of 3-methylcholanthrene (MC; 42 mg/kg, once) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 20 micrograms/kg, 6 times) in order to investigate the effect of 3-methylsulphonyl-4,5,3',4'-tetrachlorobiphenyl (3-MSF-4,5,3',4'-TCB; 1.5-45 micrograms/ml) and 7,8-benzoflavone (ANF; 1.4-42 micrograms/ml) on the hepatic microsomal AHH activities and the following results were obtained. 1. In the Ah nonresponsive strains of mice, 70 and 20% of the induced AHH activities with MC and TCDD, respectively, were attributable to the basal control enzyme activity and in the Ah responsive ones, only 4.2 and 1.4% of the induced activities with the two chemicals to the untreated control one, respectively. 2. 3-MSF-4,5,3',4'-TCB and ANF enhanced or reduced the enzyme activity depending on both their concentrations and kinds of microsomes employed, namely, control-, MC- and TCDD-microsomes. ANF showed higher potency for both the activation and inhibition of the AHH activity than 3-MSF-4,5,3',4'-TCB. 3. The effects of 3-MSF-4,5,3',4'-TCB and ANF on the enzyme activity of the MC treated Ah nonresponsive mice and those of the untreated control Ah responsive animals were quite similar and their effects on the AHH activity of the TCDD treated Ah nonresponsive strains were also almost the same as those of the MC or TCDD treated Ah responsive ones.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies in C57BL/6J, DBA/2J and C3H/HeJ mice and in two F1 hybrid strains (B6D2F1 and B6C3HF1) 2-5 months old revealed marked genotypic differences among inbred strains. C57 mice had three times as many regular (3-6 days) cycles as DBA and C3H mice, due largely to fewer pseudopregnant-like (7-14 day) cycles. C57 had longer regular cycles than DBA and C3H mice. Although the frequencies of regular cycles of DBA and C3H mice were similar, the cycles of C3H mice were shorter than those of DBA mice. The results indicated that the genetic determinants of the frequency of regular cycles differ from those specifying cycle length. Frequency of regular cycles of F1 hybrids was either intermediate between the parent strains (B6D2F1) or similar to the C57 strain (B6C3HF1), suggesting that regular cycle frequency shows additive genetic variation in the former crosses, but mostly dominant variance in the latter background. Regular cycles were either shorter than in both parent strains (B6D2F1) or similar to one of them (B6C3HF1), indicating heterosis and dominance for genes specifying short cycles. Although the lack of reciprocal crosses meant that maternal effects and possible genomic imprinting effects could not be assessed, these results reveal marked genetic influences on cycle length and frequency and suggest that some of the genes specifying these two traits differ.
The relationship between analgesia and behavior during and after an aggressive encounter was investigated in saline- and opiate antagonist-treated DBA mice. A low number of bites induced an analgesia that was reversed by beta-chlornaltrexamine but not by naloxone, and that correlated positively with increased displays of defensive upright and immobility upon contact with the opponent. Extended attacks induced a naloxone-sensitive analgesia that was linked to a delayed occurrence of "panic" escape behavior. In the post-conflict phase, the degree of immobility and analgesia correlated positively in attacked mice. Naltrexone prevented this analgesia and lowered immobility. Endogenous opioids released during social conflict may induce analgesia and immobility in DBA mice.
We carried out investigations on C3H, NMRI, C57Bl/6, Balb/c, Balb/cN, and DBA inbred mouse strains in the shuttle-box to see whether their learning behavior is genetically controlled. The highly different learning behavior of the parental strains made it possible to test the F1 hybrids and the F2 generation. The environmental influences were standardized as much as possible. In particular, influences possible during the lactation period were excluded by using foster breeding. The results enable us to postulate monogenic inheritance for the learning speed in the shuttle-box. The inheritance is interpreted as codominant. The investigations are part of a basic study in mammalian behavior genetics from the human genetic aspect.
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This study was designed to assess the possible genetic determinants of neurosensitivity to early (neonatal) phenobarbital (PhB) administration and to conduct a strain comparison for the cerebellar histology of both inbred and outbred mice. HS/Ibg, C57BL/10 and DBA/1 pups were injected with 50 mg PhB/kg daily on neonatal days 2-21. On day 50, treated animals (B) of all strains had smaller brains than controls (C). Moreover, the cerebellar area was decreased in HS and C57 B mice but not in DBA mice, suggesting genotype-environment interaction. B mice from all strains had similar Purkinje cell losses. Strain comparison showed that control C57 mice had smaller brains than control HS, and DBA had smaller brains than both HS and C57. Similarly, C57 had smaller cerebellar layers than HS and DBA had smaller cerebellar layers than both HS and C57. DBA and C57 mice had fewer Purkinje cells than HS but did not differ from each other.