Learning in year-old female autoimmune BXSB mice.

BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease. Approximately 40-60% of these animals show ectopic clusters of neurons in Layer I of cortex similar to those found in postmortem analyses of human dyslexics, and all exhibit an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans. The expression of immune disease in the BXSB strain, unlike in humans, is more severe in males than females. Most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age, when the BXSB females (unlike the male BXSB and female and male NZBs) are not yet showing high titers of autoantibodies associated with their lupus-like form of autoimmune disease. This study examined the behavior of BXSB females at an age subsequent to autoimmune disease onset. When contrasted with younger animals, year-old BXSB females showed good learning behavior, with no differences in Lashley maze learning and remarkably good performance in a visual discrimination learning task. These results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease. Results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in Lashley maze learning. Animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures. These findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals.

Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.

Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.

Antagonism of estrogenic effects on feeding behavior by central implants of anisomycin.

The following experiment determined whether the estrogenic suppression of food intake is dependent upon changes in protein synthesis within neurons of the paraventricular nucleus of the hypothalamus (PVN). Ovariectomized rats were treated centrally with anisomycin-filled or empty (control) cannulae in the PVN. Females were injected with either 2.0 micrograms of estradiol benzoate (EB) or the oil vehicle and the inner cannulae were removed 2 h later. EB injections significantly lowered food and water intake in the central control group but not in animals given PVN implants of anisomycin. Body weight gain decreased for all females. EB induced comparable levels of female sexual behavior in both groups, demonstrating that anisomycin implants did not affect the ability of estradiol to stimulate lordosis. These findings indicate that the effects of estradiol on food intake require the activation of protein synthesis in estrogen-sensitive PVN neurons.

Modulation of the satiety effect of cholecystokinin by estradiol.

Data obtained from a wide variety of mammalian species indicate that feeding behavior can be influenced by changes in endogenous estrogens and by exogenous estrogenic treatments. The present experiment represents an initial investigation of the hypothesis that the suppression of food intake by estradiol is mediated by an enhancement of the satiety effect of cholecystokinin (CCK). Twenty-four female rats were ovariectomized and implanted either with a 5% estradiol silastic capsule or an empty capsule on the day of surgery. Three weeks later, animals received IP injections of CCK-octapeptide (5.0 or 10.0 micrograms/kg) or saline after 24-h food deprivation. Food and water intake were measured 60 min after treatment. Although CCK suppressed feeding in all subjects, the effects on food intake were greater in estradiol-treated females. CCK injections also reduced water intake, but there was no interaction between estradiol and CCK on drinking. These findings indicate that the inhibitory effect of CCK on food intake is enhanced in females treated with a physiological dose of estradiol, and suggest that the effects of estradiol on feeding behavior may be mediated by a potentiation of the satiety effect of CCK.