Drug sensitization in rats prenatally exposed to methamphetamine

Methamphetamine (MA) is a psychostimulant drug with high potential for abuse. Psychostimulants were shown to cause behavioral sensitization - a progressive increase of their psychomotor activating effects. Since half of MA users are women of reproductive age, there is an increased risk of negative consequences for their children. The aim of my dissertation thesis was to find out whether prenatal MA exposure is able to increase sensitivity to the same drug in adulthood. Pregnant dams were injected daily with MA 5 mg/kg or saline (S) subcutaneously (s.c.) during the whole gestation. The absolute control group of adult females (C) was not exposed to any injection application. To test the sensitivity of the offspring to MA in adulthood, half of each prenatally exposed group (MA, S, C) were administered MA 1 mg/kg while the other half received S s.c. The sensitizing effect of prenatal MA exposure was tested in the open field, elevated plus maze, Laboras (Metris B.V., Netherlands), Morris water maze, tail-flick test and in the tests of susceptibility to epileptic seizures. Our results showed that the animals prenatally exposed to MA were more susceptible to flurothyl seizures and demonstrated better performance in the test of memory. On the other hand, acute MA application in adulthood increased motor activity,..

The circadian system in Alzheimer's disease: Disturbances, mechanisms, and opportunities

Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.Andrew N. Coogan, Barbora Schutová, Susanne Husung, Karolina Furczyk, Bernhard T. Baune, Peter Kropp, Frank Häßler, and Johannes Thom