Single injection of rapamycin blocks post-food restriction hyperphagia and body-weight regain in rats.

Given the increasing prevalence of and severity of complications associated with obesity, there is great need for treatments resulting in prolonged weight loss. Long-term maintenance of weight loss requires sustained changes in food-intake and energy-expenditure strategies, which are unfortunately often taxing, resulting in a return to predieting weight. Therefore, drug therapies may facilitate greater adherence to a restricted diet and prolong weight loss.

Absence of neurogenic response following robust predator-induced stress response.

Traumatic events contribute to a variety of neuropsychiatric disorders including post-traumatic stress disorder (PTSD). Identifying the neural mechanisms that affect the stress response may improve treatment for stress-related disorders. Neurogenesis, the production of neurons, occurs within the adult brain and disturbances in neurogenesis in the subgranular zone (SGZ) of the hippocampus have been linked to mood and anxiety disorders.

Time-dependent effects of rapamycin on consolidation of predator stress-induced hyperarousal.

Previous studies have indicated that rapamycin, a potent inhibitor of the mammalian target of rapamycin (mTOR) pathway, blocks consolidation of shock-induced associative fear memories. Moreover, rapamycin's block of associative fear memories is time-dependent. It is unknown, however, if rapamycin blocks consolidation of predator stress-induced non-associative fear memories.

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.

Systemic inhibition of mTOR kinase via rapamycin disrupts consolidation and reconsolidation of auditory fear memory.

The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA translation and is known to be involved in various long lasting forms of synaptic and behavioural plasticity. However, information concerning the temporal pattern of mTOR activation and susceptibility to pharmacological intervention during both consolidation and reconsolidation of long-term memory (LTM) remains scant. Male C57BL/6 mice were injected systemically with rapamycin at various time points following conditioning or retrieval in an auditory fear conditioning paradigm, and compared to vehicle (and/or anisomycin) controls for subsequent memory recall.

Inhibition of mTOR kinase via rapamycin blocks persistent predator stress-induced hyperarousal.

Traumatic, stressful life events are thought to trigger acquired anxiety disorders such as post-traumatic stress disorder (PTSD). Recent data suggests that the mammalian target of rapamycin (mTOR) plays a key role in the formation of traumatic memories. The predator stress paradigm allows us to determine whether mTOR mediates the formation of both context-dependent (associative) and context-independent (non-associative) fear memories.

Dendritic morphology of amygdala and hippocampal neurons in more and less predator stress responsive rats and more and less spontaneously anxious handled controls.

We investigated the neurobiological bases of variation in response to predator stress (PS). Sixteen days after treatment (PS or handling), rats were grouped according to anxiety in the elevated plus maze (EPM). Acoustic startle was also measured.

Glucocorticoids are required for extinction of predator stress-induced hyperarousal.

Background: The role of glucocorticoids in extinction of traumatic memories has not been fully characterized despite its potential as a therapeutic target for acquired posttraumatic stress disorder (PTSD). The predator stress paradigm allows us to determine whether glucocorticoids mediate the extinction of both context-dependent and context-independent fear memories.

Methods: Male C57BL/6J mice were exposed to a predator (cat) then repeatedly exposed to the predator stress context in the absence of the cat.

Long lasting effects of predator stress on pCREB expression in brain regions involved in fearful and anxious behavior.

Predator stress is one animal model of posttraumatic stress disorder (PTSD). Neural plasticity in amygdala afferent and efferent pathways underlies anxiogenic effects of predator stress. Predator stress increases pCREB expression in these pathways 20min after stress, implicating pCREB in stress-induced neural plasticity.