Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat

RationaleEffort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue, are an important aspect of depression and other disorders. Motivational symptoms are resistant to some treatments, including serotonin transport (SERT) inhibitors.Objectives Tests of effort-based choice using operant behavior tasks (e.g., concurrent lever pressing/ chow feeding tasks) can be used as animal models of motivational symptoms. Tests of effort-related choice allow animals to choose between high-effort actions that lead to more highly valued rewards vs. low-effort alternatives that lead to less valued rewards (i.e., less preferred or lower magnitude). Rats treated with the vesicular monoamine transport inhibitor tetrabenazine, or the cytokine interleukin-1β (IL-1β), which are associated with depressive symptoms in humans, can alter effort-related choice, reducing selection of the high effort alternative (lever pressing) while increasing intake of freely available chow.MethodsThe present studies focused upon the ability of lisdexamfetamine (LDX) to increase exertion of effort in rats responding on effort-based choice tasks under several different conditions.ResultsLDX attenuated the shift from fixed ratio 5 lever pressing to chow intake induced by tetrabenazine and IL-1β. In contrast, the SERT inhibitor s-citalopram failed to reverse the effects of tetrabenazine. When given in combination with tetrabenazine+s-citalopram, LDX significantly increased lever pressing output compared to tetrabenaine+citalopram alone. LDX also increased work output in rats responding on a progressive ratio/chow feeding choice task.ConclusionsLDX can increase work output in rats responding on effort-based choice tasks, which may have implications for understanding the neurochemistry of motivational symptoms in humans

The impact of 36 years of grazing management on soil nitrogen (N) supply rate and Salix repens N status and internal cycling in dune slacks

The final publication is available at Springer via http://dx.doi.org/10.1007/s11104-015-2628-9Aims: To determine the impact of long-term rabbit and sheep grazing on Salix repens N status (green and abscised leaf N content and C:N ratio), internal N dynamics and soil N supply rate in dune slacks. Methods: Herbivore exclosures were erected in dune slacks at Ainsdale Sand Dunes NNR, creating three grazing treatments: rabbit grazing; rabbits excluded for 36 years; rabbit grazing followed by sheep and rabbit grazing for 18 years. Soil N supply rate was analysed using ion exchange membranes; leaf N dynamics of S. repens were measured over one summer. Results: Soil N supply rate was higher in ungrazed plots. There was no difference in green leaf N<inf>MASS</inf> or C:N ratio between treatments, but N dynamics differed. Adding sheep to existing rabbit grazing reduced S. repens N resorption efficiency (R<inf>EFF</inf>) from 67 to 37 %; excluding rabbits had no impact. Litter N<inf>MASS</inf> was lower and C:N ratio higher in ungrazed plots. Conclusions: Grazing can impact significantly on leaf N resorption, but this impact depends on the grazing regime

The pharmacology of effort-related choice behavior: Dopamine, depression, and individual differences

This review paper is focused upon the involvement of mesolimbic dopamine (DA) and related brain systems in effort-based processes. Interference with DA transmission affects instrumental behavior in a manner that interacts with the response requirements of the task, such that rats with impaired DA transmission show a heightened sensitivity to ratio requirements. Impaired DA transmission also affects effort-related choice behavior, which is assessed by tasks that offer a choice between a preferred reinforcer that has a high work requirement vs. less preferred reinforcer that can be obtained with minimal effort. Rats and mice with impaired DA transmission reallocate instrumental behavior away from food-reinforced tasks with high response costs, and show increased selection of low reinforcement/low cost options. Tests of effort-related choice have been developed into models of pathological symptoms of motivation that are seen in disorders such as depression and schizophrenia. These models are being employed to explore the effects of conditions associated with various psychopathologies, and to assess drugs for their potential utility as treatments for effort-related symptoms. Studies of the pharmacology of effort-based choice may contribute to the development of treatments for symptoms such as psychomotor slowing, fatigue or anergia, which are seen in depression and other disorders