Single rapamycin administration induces prolonged downward shift in defended body weight in rats.

Manipulation of body weight set point may be an effective weight loss and maintenance strategy as the homeostatic mechanism governing energy balance remains intact even in obese conditions and counters the effort to lose weight. However, how the set point is determined is not well understood. We show that a single injection of rapamycin (RAP), an mTOR inhibitor, is sufficient to shift the set point in rats. Intraperitoneal RAP decreased food intake and daily weight gain for several days, but surprisingly, there was also a long-term reduction in body weight which lasted at least 10 weeks without additional RAP injection. These effects were not due to malaise or glucose intolerance. Two RAP administrations with a two-week interval had additive effects on body weight without desensitization and significantly reduced the white adipose tissue weight. When challenged with food deprivation, vehicle and RAP-treated rats responded with rebound hyperphagia, suggesting that RAP was not inhibiting compensatory responses to weight loss. Instead, RAP animals defended a lower body weight achieved after RAP treatment. Decreased food intake and body weight were also seen with intracerebroventricular injection of RAP, indicating that the RAP effect is at least partially mediated by the brain. In summary, we found a novel effect of RAP that maintains lower body weight by shifting the set point long-term. Thus, RAP and related compounds may be unique tools to investigate the mechanisms by which the defended level of body weight is determined; such compounds may also be used to complement weight loss strategy.

Cytotoxic lesions of the hippocampus do not impair social recognition memory in socially housed rats.

Socially housed mice with cytotoxic lesions of the hippocampus do not exhibit social recognition memory 30 min following exposure to a juvenile mouse, however the social recognition memory of singly housed rats is unimpaired. The present study tests the hypothesis that social housing of rats could render social recognition memory hippocampally dependent as seen for mice. Rats were housed with juveniles or with adults. Two social recognition one-animal tests paralleling those used with mice were carried out. Seven social discrimination two-animal tests were also given. Sham operated and hippocampally lesioned rats had normal social memory at 30 min whether socially housed for 24, 48 h, 7 or 8 days prior to testing. These findings support other results indicating the hippocampus proper is not required for normal social memory in rats. In a final experiment, rats socially housed in groups of three since weaning, were tested for 30 min and 24 h social memory. Unlike mice, rats socially housed throughout life exhibited social memory only at 30 min, but not at 24 h. Manipulations that extend social memory in rats may be required to render social memory hippocampally dependent or rats and mice may differ in the neural mediation of social memory.