Altered polyamine metabolism in the PRO/Re strain of inbred mice

The PRO/Re strain of inbred mice are characterized by abnormally high concentrations of proline in both blood (hyperprolinaemia) and urine (prolinuria). They excrete increased amounts of polyamines in their urine. Male PRO/Re mice excreted putrescine at 175% and spermidine at 300% the amount of male C57BL/6J controls. Female PRO/Re mice excreted putrescine at 115% and spermidine at 150% of the amount in the urine of female controls. Examination of the enzymes involved in polyamine biosynthesis revealed that ornithine decarboxylase, the initial enzyme in the polyamine-biosynthetic pathway, was increased by 150% in the kidneys and by 100% in the liver of male PRO/Re mice. There was no significant difference between PRO/Re and C57BL/6J male mice for either putrescine- or spermidine-stimulated S-adenosylmethionine decarboxylase activity. Female PRO/Re mice showed no significant difference from female C57BL/6J mice for any of the enzymes examined. When the concentrations of the polyamines in the tissues of the PRO/Re mice were determined, spermidine and spermine concentrations in the kidneys of the male PRO/Re mice were twice those of the controls. Spermidine concentration in the livers of both male and female PRO/Re mice was approx. 130% that of the controls. Polyamine concentrations in the brains were similar in controls and mutants. The increased polyamine biosynthesis and excretion in the PRO/Re mutant mice may be a mechanism to decrease the extent of proline accumulation.     

Behavioral and neuroendocrine reactivity to stress in the WKHA/WKY inbred rat strains: a multifactorial and genetic analysis

Genetic factors have been shown to influence the nature and the intensity of the stress responses. In order to understand better the genetic mechanisms involved, we have studied the behavioral and neuroendocrine responses to novel environments in the WKHA/WKY inbred strains and we have investigated the genetic relationships between these traits in a segregating F2 intercross. The animals were submitted to behavioral tests known to provide both indices of activity and fear (activity cages, open field and elevated plus-maze). The plasma levels of prolactin, ACTH, corticosterone, glucose and renin activity were determined after a 10-min exposure to novelty. Our results showed that WKHA rats, compared to WKYs, were more active in a familiar as well as in novel environments. They exhibited also less anxiety-related behaviors and lower neuroendocrine responses. A principal component analysis performed on the behavioral F2 results defined three independent factors: general activity, anxiety and defecation, none of them being correlated with the neuroendocrine measures. Thus this study suggests that these different responses to stress are independent components that may have distinct molecular bases.     

Genetics ethanol and the Fos response: a comparison of the C57BL/6J and DBA/2J inbred mouse strains

The effect of ethanol (0.25 to 4 g/kg) on the number of Fos-like immunoreactive (Fos-li) neurons was studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The brain regions emphasized in the analysis were from the basal ganglia and some associated limbic nuclei. The question addressed was whether or not the D2 and B6 strains differed in these regions in a way that could explain the marked psychomotor stimulation of the D2, but not the B6, strain over the dose range of 1 to 2 g/kg of ethanol. Over the dose range of 0.25 to 2 g/kg, ethanol caused a modest increase in the number of Fos-li neurons within the caudate putamen (dorsolateral and dorsomedial) and the nucleus accumbens (core and shell), but there were no marked strain effects. There was no significant effect in either strain of ethanol treatment (0.25 to 2 g/kg) in the globus pallidus, ventral pallidum, and subthalamic nucleus. However, at 4 g/kg, there was a dramatic (> 100%) increase of Fos-li neurons in the D2 but not B6 strain. A similar effect was noted in the entopeduncular nucleus, the substantia nigra zona reticulata (and compacta), but not the ventral tegmental area. A marked and substantial (> 200%) Fos response was seen in the central amygdaloid nucleus (CeA) of the D2 strain over the entire dose range; in contrast, a substantial Fos response in the B6 strain was seen only at the 4 g/kg dose. The paraventricular thalamic nucleus, in general, paralleled data in the CeA; but, the Fos response was more modest, and the results for the D2 strain were significant only at the 2 g/kg dose. Overall, data suggest that ethanol at low to moderate doses induces significant, strain-dependent Fos responses in some limbic structures, but not in the basal ganglia. The possibility is considered that activation of some neurons in the CeA are permissive for expression of the ethanol-induced increase in motor activity.     

Behavioral differences between two inbred strains of Fawn-Hooded rat: a model of serotonin dysfunction

The Fawn-Hooded rat (FH) strain has attracted the attention of some psychopharmacologists because of reports of its exaggerated immobility in the swim test, hypercortisolemia, excessive voluntary intake of alcohol, platelet and central serotonin abnormalities and subsensitivity to serotonergic agonists. However, there appears to be some controversy over several behavioral and physiological characteristics of these rats. The present paper proposes that the lack of reproducible findings can be traced to there being several distinct inbred strains of FH rats. Of the two compared in this communication, the FH/Wjd strain is more immobile in the forced swim test, spends more time in the open arms of the elevated plus maze, and drinks more saccharin and alcohol voluntarily than the FH/Har (Iowa Reactive) strain. Future workers are cautioned to report the source of their FH rats.     

Ultrafast freezing of the embryos of outbred and inbred mouse strains

Prophylaxis of postoperative thromboembolism is widely used because it has been shown to save lives and money. However, some surgeons are still reluctant to use general prophylaxis in high-risk orthopedic surgery. In total hip and total knee replacement the best method of prophylaxis is currently low molecular weight heparin started preoperatively and continued for 7 to 14 days or until the patient is fully ambulatory. A shorter prophylaxis period failed to be effective in an English study. At present there is an ongoing debate on the length of the period of risk, and whether there is a need for prophylaxis after discharge. Oral anticoagulation has been used for extended prophylaxis, but studies show that anticoagulant levels need to be monitored by repeated measurements by international normalized ratio. An alternative method would be to continue low molecular weight heparin injections for 4 to 5 weeks after surgery. No studies so far have evaluated the efficacy and safety of prolonged prophylaxis with low molecular weight heparin after discharge.     

Behavioural performance in three substrains of mouse strain 129

Recently, the possibility has been raised that the behavioural abnormalities seen in null-mutant mice might be determined by their genetic background rather than by loss of gene function, especially when the 129 mouse strain is used as supplier for embryonic stem (ES) cells. To examine this issue we tested three 129 mouse substrains (129/J, 129/Ola, 129/Sv-ter/+) and C57BL/6 (B6) in the Morris water maze, the open field, the plus maze and two tests assessing motor co-ordination. We identified only for the 129/J substrain substantial behavioural deficits. These mice are albinos and carry the pink-eyed dilution allele and differed in their basal anxiety level as assessed in the open-field test. They were severely impaired in spatial learning and memory (Morris water maze test), in the Porsolt swim test, which also measures learning and in motor co-ordination. However, the 129/J substrain has not been used as ES cell donor in null-mutant mice where behavioural abnormalities were observed. Instead, mice from 129/Ola and 129/Sv-ter/+ substrains have been commonly used as suppliers for ES cells. These performed normally in most of the tests, including Morris water maze test.     

Newborn organ weight and spontaneous hypertension: recombinant inbred strain study

This study investigated the effects of neonatal hippocampal ablation on the development of spatial learning and memory abilities in rats. Newborn rats sustained bilateral electrolytic lesions of the hippocampus or were sham-operated on postnatal day 1 (PN1). At PN20-25, PN50-55, or PN90-95, separate groups of rats were tested in a Morris water maze on a visible "cue" condition (visible platform in a fixed location of the maze), a spatial "place" condition (submerged platform in a fixed location), or a no-contingency "random" condition (submerged platform in a random location). Rats were tested for 6 consecutive days, with 12 acquisition trials and 1 retention (probe) trial per day. During acquisition trials, the rat's latency to escape the maze was recorded. During retention trials (last trial for each day, no escape platform available), the total time the rat spent in the probe quadrant was recorded. Data from rats with hippocampal lesions tested as infants (PN20-25) or as adults (PN50-55 and PN90-95) converged across measures to reveal that 1) spatial (place) memory deficits were evident throughout developmental testing, suggesting that the deficits in spatial memory were long-lasting, if not permanent, and 2) behavioral performance measures under the spatial (place) condition were significantly correlated with total volume of hippocampal tissue damage, and with volume of damage to the right and anterior hippocampal regions. These results support the hypothesis that hippocampal integrity is important for the normal development of spatial learning and memory functions, and show that other brain structures do not assume hippocampal-spatial memory functions when the hippocampus is damaged during the neonatal period (even when testing is not begun until adulthood). Thus, neonatal hippocampal damage in rats may serve as a rodent model for assessing treatment strategies (e.g., pharmacological) relevant to human perinatal brain injury and developmental disabilities within the learning and memory realm.     

Fear-potentiated startle in two strains of inbred mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of this study was to examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and DBA/2J (DBA) mice were given tone?+?foot shock training trials. The amplitude of the acoustic startle reflex was measured in the presence and absence of the tone both before and after training. Both strains showed fear-potentiated startle after training as evidenced by larger startle amplitudes in the presence of the tone than in its absence. However, the magnitude of fear-potentiated startle was greater in DBA mice than in C57 mice. These results not only demonstrate fear-potentiated startle in mice for the first time but also suggest that fear-potentiated startle can be influenced by characteristics of the mouse strain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.

Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 ± 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nucleic acid concentration in the brains of inbred rats of different strains

The changes of nucleic acids content in the formation of conditioned skin-defence reflex was studied on inbred rats of various strains. In WGA rats the reflex was formed on the average aight stimulations. An increased RNA content was discovered by cytophotometric determination of the nucleic acids content in the neurons and perineural glia of the cerebral cortex in August rats only. It is assumed that an increased RNA synthesis in the animals of this strain can serve as the basis for their better training.     

Genotype dependence of monoamine oxidase in inbred strains of mice

MAO activity was found to be influenced by the genotype or strain of mouse up to 20 days of age. The strain differences observed may derive from different rates of brain development. A number of neurological mutations comprizing three pathological classes had no effect on MAO.     

Genetics, haloperidol, and the Fos response in the basal ganglia: a comparison of the C57BL/6J and DBA/2J inbred mouse strains

The haloperidol-induced increase of Fos-like immunoreactive (Fos-li) neurons in the basal ganglia was compared in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The D2 strain is 10-fold more sensitive than the B6 strain to haloperidol-induced catalepsy, a putative animal model of the extrapyramidal symptoms (EPS) seen after the administration of typical neuroleptics. In contrast, the strains are equally sensitive to the haloperidol facilitation of prepulse inhibition of the acoustic startle response, a measure of drug efficacy on the mesolimbic dopamine system. The haloperidol effects on Fos-li neurons were examined over the range of 0.1 to 6.0 mg/kg; the ED50s for haloperidol-induced catalepsy are 0.4 and 3.8 mg/kg in the D2 and B6 strains, respectively. In neither the core or shell of the nucleus accumbens nor the caudate-putamen (including the dorsolateral aspect) did the D2 strain show a greater Fos response compared to the B6 strain. In fact, in the dorsolateral caudate-putamen, the B6 strain showed a modest but significantly greater Fos response. However, at the output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra zona reticulata (SNr), the D2 strain consistently showed a greater Fos response. These data suggest that the EP and SNr may be important to understanding the difference in haloperidol-induced catalepsy between the D2 and B6 strains.     

Primary aggressive motivation in three inbred strains of mice.

30 male mice from 3 inbred strains (BALB/cJ, RF/J, and SJL/J), isolated since 35 days of age, were run at 135 days in a T maze, and acquired a position response when the opportunity to attack a nonaggressive S was used as a reinforcer. Results are interpreted as evidence for primary intraspecific aggressive motivation. Strain differences were significant. Significant warm-up effects were also obtained, including persistent increases in number of correct T-maze choices from 1st to later trials given each day. An identically composed group of 30 food-deprived Ss were run in the maze for food reward. Eating was uniformly a highly effective reinforcer. However, in the 2 best-performing strains the effectiveness of aggression reinforcement following warm-up approached that of reinforcement by eating. (26 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: comparison of inbred strains

PURPOSE: Previous work from our laboratory showed that amygdala-kindled Wistar outbred rats can be selected according to the increase of afterdischarge threshold (ADT) after phenytoin application. Animals that consistently do not respond to phenytoin (PHT) with an ADT increase (non-responders) are the first animal model of pharmacoresistant complex partial seizures. In this study, we determined the ability to respond to PHT in male kindled rats of different inbred strains. METHODS: The experiments were performed in fully kindled rats of five different inbred strains, Wistar-Kyoto, Lewis, Fischer 344, ACI, and Brown Norway. The response type of each rat was revealed by four consecutive PHT applications (75 mg/kg, i.p.) in fully kindled rats. RESULTS: PHT application resulted in plasma concentrations ranging from some 16 microg/ml in Lewis rats to 35 microg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer 344 rats. The rats of each strain did not show a homogeneous response to PHT. A significant increase of ADT was found after 86-97% of applications in Lewis, Wistar-Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in only 34% of experiments. This led to a considerable number of responders (i.e., consistent ADT increase by >20%) in Fischer 344, Wistar-Kyoto, and Lewis rats. The only strain revealing nonresponders (i.e., consistent lack of ADT increase by >20% with PHT treatment) was Brown Norway. CONCLUSIONS: Inbred strains, although genetically more homogenous than outbred strains, differ in their response to PHT. Brown Norway rats can offer advantages for further detailed investigation of the resistance to PHT in the kindling model of complex partial seizures.     

Fear conditioning in inbred mouse strains: An analysis of the time course of memory.

Three mouse strains were examined for short- and long-term memory for Pavlovian fear conditioning measured 1 hr and 24 hr after conditioning. Both DBA/2J and CBA/J mice exhibit reduced long-term memory for contextual fear conditioning compared with C57BL/6J mice. In cued fear conditioning, however, DBA/2J mice show reduced short- and long-term memory compared with C57BL/6J mice, whereas CBA/J mice exhibit reductions only in short-term memory. These results underscore the importance of examining the time course of memory retention, and they suggest that inbred mouse strains may provide a diversity of phenotypes. The results also suggest that the processes of short- and long-term memory storage as well as contextual and cued fear conditioning are dissociable and are mediated by genetically distinct neurobiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)