Estradiol to aged female or male mice improves learning in inhibitory avoidance and water maze tasks.

Although 17beta-Estradiol (E2) improves cognitive performance of aged female mice, its mnemonic effects when administered post-training to aged male mice have not been examined. E2 (10 microg, SC) or oil vehicle was administered to intact, 24-month-old female or male congenic (primarily C57BL/6 background) mice immediately after training in the inhibitory avoidance or water maze tasks. Following behavioral testing, effects of 1 or 24 h of E2 exposure on hippocampal levels of E2 and brain-derived neurotrophic factor (BDNF) were examined. Female and male mice administered E2 showed significantly better performance in the inhibitory avoidance task than did vehicle-administered mice. When tested 24 h after training, mice that received E2 had significantly longer latencies to cross-over to the shock-associated side of the chamber than did vehicle-administered mice. Female or male mice administered E2 showed significantly better performance in the reference memory aspect of the spatial water maze task. When tested 30 min after training, mice administered E2 had shorter latencies to, and spent longer swimming in, the quadrant that the hidden platform had previously been located in. E2 administration produced physiological levels of E2 in the hippocampus 1 and 24 h after E2. BDNF levels in the hippocampus were decreased following 1 h of E2 exposure compared to vehicle. These findings suggest that E2 to female and male mice may overcome age-related deficits in reference memory in an emotional or spatial learning task.

Genetic variation in the psychomotor stimulant properties of cocaine in Mus musculus.

RATIONALE: The psychomotor stimulant properties of drugs are argued to be a key feature of abuse liability. Several studies, primarily using inbred strains of mice, have demonstrated genetic variation in the psychomotor stimulant properties of cocaine. As of yet, however, no gene(s) has been identified which influences this phenotype. OBJECTIVES: The purpose of the present study was to examine a number of inbred strains of mice, including several closely related substrains, for cocaine-induced locomotor activation. Such substrain differences would suggest the possibility of a major gene effect. These data will also help to further characterize the range of genetic variation in response to cocaine. METHODS: Mice from 11 inbred strains were initially injected with saline and activity monitored for 30 min; mice were then removed from the activity monitor, injected with saline or one of six doses of cocaine, and activity was monitored for an additional 30 min. RESULTS: Compared to several other closely related C57BL substrains, we found the C57BL/10SnJ substrain to be significantly less activated following cocaine administration. In contrast, the C57BR/cdJ and C57L/J substrains showed extremely high levels of cocaine-induced locomotor activation. CONCLUSIONS: The genetic similarity between C57BL/10SnJ and the other closely related C57BL substrains suggests the possibility that the aberrant behavioral response to cocaine observed in B10SnJ mice may be due to a major gene effect. Similarly, the differences found in the C57BR/cdJ and C57L/J substrains may also be influenced by a major gene. The strains examined in this study will be useful tools for identification of relevant quantitative trait loci.

Different data from different labs: lessons from studies of gene-environment interaction.

It is sometimes supposed that standardizing tests of mouse behavior will ensure similar results in different laboratories. We evaluated this supposition by conducting behavioral tests with identical apparatus and test protocols in independent laboratories. Eight genetic groups of mice, including equal numbers of males and females, were either bred locally or shipped from the supplier and then tested on six behaviors simultaneously in three laboratories (Albany, NY; Edmonton, AB; Portland, OR). The behaviors included locomotor activity in a small box, the elevated plus maze, accelerating rotarod, visible platform water escape, cocaine activation of locomotor activity, and ethanol preference in a two-bottle test. A preliminary report of this study presented a conventional analysis of conventional measures that revealed strong effects of both genotype and laboratory as well as noteworthy interactions between genotype and laboratory. We now report a more detailed analysis of additional measures and view the data for each test in different ways. Whether mice were shipped from a supplier or bred locally had negligible effects for almost every measure in the six tests, and sex differences were also absent or very small for most behaviors, whereas genetic effects were almost always large. For locomotor activity, cocaine activation, and elevated plus maze, the analysis demonstrated the strong dependence of genetic differences in behavior on the laboratory giving the tests. For ethanol preference and water escape learning, on the other hand, the three labs obtained essentially the same results for key indicators of behavior. Thus, it is clear that the strong dependence of results on the specific laboratory is itself dependent on the task in question. Our results suggest that there may be advantages of test standardization, but laboratory environments probably can never be made sufficiently similar to guarantee identical results on a wide range of tests in a wide range of labs. Interpretations of our results by colleagues in neuroscience as well as the mass media are reviewed. Pessimistic views, prevalent in the media but relatively uncommon among neuroscientists, of mouse behavioral tests as being highly unreliable are contradicted by our data. Despite the presence of noteworthy interactions between genotype and lab environment, most of the larger differences between inbred strains were replicated across the three labs. Strain differences of moderate effects size, on the other hand, often differed markedly among labs, especially those involving three 129-derived strains. Implications for behavioral screening of targeted and induced mutations in mice are discussed.