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Serotonergic influence on cholinergic-induced analgesia: differences in two inbred strains of mice.

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.

Acetylcholine

Inheritance of discrimination learning ability and retention in BA and DBA mice.

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.

Animals

Biphasic effects of ethanol on open-field activity: sensitivity and tolerance in C57BL/6N and DBA/2N mice.

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.

Animals

Strain-dependent effects of naloxone on discrimination learning in mice.

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.

Animals

Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages.

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.

Aging

Effects of 3-methylsulphonyl-4,5,3',4',-tetrachlorobiphenyl and 7,8-benzoflavone on aryl hydrocarbon hydroxylase activities of murine hepatic microsomes prepared from inbred strains with different Ah responsiveness.

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)

Animals

Genetic influences on oestrous cyclicity in mice: evidence that cycle length and frequency are differentially regulated.

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.

Animals

Relationship between behavioral and nociceptive changes in attacked mice: effects of opiate antagonists.

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.

Animals

Monogene inheritance of learning speed in DBA and C3H mice. A behavioral genetic study in the shuttle-box.

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.

Animals

Genetic factors influencing neurosensitivity to early phenobarbital administration in mice.

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.

Animals

Developmental differences of antinociceptive effects of oxotremorine in two inbred strains of mice.

During development the C57BL/6 and DBA/2 mouse strains present morphological variations in cholinergic forebrain structures correlated with different behavioral reactivities to cholinergic agents. The present research assessed that these strain-dependent differences are also present in cholinergic-mediated analgesia. The administration of oxotremorine (0.0025, 0.005 and 0.01 mg/kg) to 30- and 60-day-old C57 and DBA mice resulted in dose- age- and strain-dependent analgesia. In particular oxotremorine is more effective in DBA/2 than in C57BL/6 mice and the latter strain showed a significant decrease of analgesic response in adulthood.

Aging

Strain differences in amiloride inhibition of NaCl responses in mice, Mus musculus.

The effects of lingual treatment with amiloride, an inhibitor of salt taste responses in several mammalian species, on NaCl responses of the chorda tympani nerve were compared between four inbred strains of mouse (BALB/cCrSlc, DBA/2CrSlc, C57BL/6CrSlc and C3H/HeSlc). In C57BL and C3H mice amiloride significantly suppressed responses of the chorda tympani nerve to NaCl at a concentration 0.1 M or more whereas in BALB and DBA mice the drug did not significantly affect the responses to NaCl at any concentration, suggesting a lack of the amiloride-sensitive receptor component for NaCl in the latter two strains. A two-bottle preference test demonstrated that all strains of mouse usually showed no preference for NaCl at any concentration and avoided NaCl at 0.3 M or more, although some differences were observed in that C57BL and C3H mice showed aversive responses to 0.1 and 0.15 M NaCl, whereas BALB and DBA mice were indifferent to these solutions. The results suggest that there exist prominent differences between mouse strains in the amiloride-sensitive component of their salt receptor systems. However, in mice the taste information derived from the amiloride-sensitive receptor component probably has no remarkable effect on behavioral responses to NaCl except for a possible contribution to decreasing aversion thresholds for NaCl by increasing overall taste information about NaCl.

Amiloride

gamma-Aminobutyric acid in brain areas of isolated aggressive or non-aggressive inbred strains of mice.

In order to investigate the effects of social isolation on aggressive behavior and GABA levels in different brain areas, inbred mice of the C57 Bl/6 and the DBA/2 strains were housed individually over a period of 8 weeks. Social isolation induced a clear increase of aggressive responses only in the DBA/2 strain and a decrease of GABA levels in septum, striatum, olfactory bulb and posterior colliculus in both the C57Bl/6 and in the DBA/2 strains. An increase of neurotransmitter concentration was observed in amygdala of DBA mice. DBA mice when compared to C57 mice showed significantly lower levels of GABA in olfactory bulb and striatum. These results are discussed in light of several previous studies which have pointed out a correlation between a deficiency of GABA mediated inhibition in some brain areas and different kinds of aggressive behavior as well as the possibility of a blockade of aggressive behavior by potentiation of GABAergic mediated inhibition. A possible suggestion emerging from our results is that the aggressive responses exhibited by isolated DBA mice but not by isolated C57 mice may be related to lower levels of the inhibitory neurotransmitter in the olfactory bulb and striatum.

Aggression

Audiogenic priming in DBA/2J and C57BL/6J mice: interactions among age, prime-to-test interval and index of seizure.

C57BL/6J mice, not susceptible to audiogenic seizures (AGS) on the 1st exposure to an acoustic stimulus, were exposed to the acoustic stimulus for 1 min and then tested at some later date (acoustic priming). They were first exposed at either 8, 16, 19, 22, or 28 days of age, and then tested for AGS 2-16 days after priming. DBA/2J mice, susceptible to AGS on the 1st exposure to intense noise, were exposed to the acoustic stimulus at 26 days of age, and then again 2-14 days later. Data indicate that the incidence of AGS upon the 2nd exposure to the acoustic stimulus is a function of age at priming, the prime-to-test interval in days, and the index of seizures. In the case of DBA mice, later effects are also dependent on the initial level of seizure.

Acoustic Stimulation