Directly to content
  1. Publishing |
  2. Search |
  3. Browse |
  4. Recent items rss |
  5. Open Access |
  6. Jur. Issues |
  7. DeutschClear Cookie - decide language by browser settings

Impact of Endocannabinoid Signaling on Cognitive Processing throughout Adolescence and Adulthood

Goepfrich, Anja Aloysia

[img]
Preview
PDF, English
Download (1MB) | Terms of use

Citation of documents: Please do not cite the URL that is displayed in your browser location input, instead use the DOI, URN or the persistent URL below, as we can guarantee their long-time accessibility.

Abstract

The present thesis investigated the basal cognitive abilities, the influence of the endocannabinoid system (ECS), and developmental aspects throughout the adolescence in male Wistar rats. First, possible behavioral differences in three different lines of Wistar Han rats were analyzed and the W[rcc] line was selected for the subsequent experiments based on its best performance in the object recognition test and good performance in the prepulse inhibition (PPI) of the acoustic startle reflex (ASR). In the second project the basic ontogeny of various cognitive abilities was analyzed and the results revealed differential patterns of development across adolescence and early adulthood. Object recognition memory showed a non-linear development with a decrease in performance on postnatal (pd) 40, at the approx. onset of puberty. This decrease was ameliorated by the administration of the cannabinoid receptor 1 (CB1R) antagonist/inverse agonist SR141716 indicating an involvement of the developing ECS at this time point. Recency discrimination developed later than recognition memory but did not display variations across adolescence. In contrast, PPI of the ASR developed gradually revealing a continuing increase of startle amplitude and sensorimotor gating abilities until early adulthood (pd 100). Molecular analysis showed increased CB1R levels in the hippocampus (Hip) in early adolescence indicating an increased ECS around that age. Myelination, which is linked to improved cognitive skills, appeared to increase gradually in the Hip and in the caudate putamen (CPu). Altogether, different cognitive abilities displayed differential time-courses of development and alterations of the developing ECS are implicated underlying some of these behavioral patterns. Long-term effects of a chronic pubertal WIN 55,212-2 treatment on cognitive abilities in adulthood included a decreased object recognition memory in the W[rcc] line, which confirmed this animal model of schizophrenia for this rat line. Moreover, complex cognitive skills were investigated in an attentional set shift test (ASST) and an impaired reversal learning ability was found while other learning abilities did not differ from vehicle treated animals. This indicates specific deficits in reversal learning upon chronic interference with the developing ECS. Furthermore, molecular analysis showed increased CB1R levels in the medial prefrontal cortex (mPFC) indicating a possible developmental compensatory mechanism in this brain region after disturbances in this particular developmental time-window. In the fourth project no long-term effects of a chronic pubertal methylphenidate (MPH) treatment on various behavioral tests were observed in adulthood for locomotor activity, anxiety-related behavior, intake of liquids of variable palatability or cognitive processing. Thus, the presently employed MPH administration paradigm did not appear to cause long-term effects but further investigations may reveal other time-windows of vulnerability to MPH administration during development. Altogether, the present thesis revealed differential developmental patterns of cognitive abilities during adolescence of male Wistar rats which appear to be linked to the developing ECS and interference with this system at this vulnerable time period may impair cognitive skills in adulthood.

Item Type: Dissertation
Supervisor: Schneider, PD Dr. Miriam
Date of thesis defense: 10 November 2014
Date Deposited: 25 Nov 2014 09:03
Date: 2014
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
About | FAQ | Contact | Imprint |
OA-LogoDINI certificate 2013Logo der Open-Archives-Initiative