Previous studies evidenced in rats that amphetamine administration immediately after the exposure to different stressors decreases the activation of the hypothalamic-pituitary-adrenal axis (HPA), as well as the hyperglycemia (index of activation of the sympathetic medullary adrenal axis) caused by exposure to stress. The effect is located at the CNS level. _x000D_ The purposes of the present Thesis have been to extend the study of the interaction between stress and amphetamine and specially to demonstrate that methylphenidate (MPH), the most used stimulant in the treatment of the attention deficit- hyperactivity disorder (ADHD), is also able to reduce, at relevant therapeutic doses, the biological and behavioral response to emotional stress._x000D_ The studies have been conducted in male adult rats (2-3 months of age), except in one experiment aimed to compare the effects of MPH in young and adult animals. Results with amphetamine indicate, in agreement with previous data, that the drug reduces in a dose-dependent way, the physiological response to the forced swim. But, moreover, this negative interaction between both stimuli also acts in the opposite manner, in a way that the exposure to stress reduces the HPA activation caused by amphetamine. In a series of experiments conducted with MPH we have demonstrated that the drug by itself does not modify the HPA axis, but, in the same way than amphetamine, is able to reduce the physiological response to stress (forced swim) when the drug is given immediately before stress. The effect is evidenced at the CNS level (CRF gene expression, the main factor that regulates the HPA axis), is observed in both young and adult animals and it is also detected when the drug is administered 30 min before exposure to stress. The protective effects of MPH are observed not only at the physiological level but also at the behavioral level in a two-way active avoidance/escape task, with an improvement in the learning and with lower levels of contextual fear conditioning. All together, the results show, for the first time, a protective effect of MPH in front of the effects of stress, having important clinical implications.
¿Puede el metilfenidato atenuar el impacto del estrés? Un modelo experimental en rata
Gagliano , H. (Author). 29 Jan 2016
Student thesis: Doctoral thesis
Student thesis: Doctoral thesis