Master Thesis in Neurobiology (2007)
The research on “an animal model for AD/HD – the Spontaneously Hypertensive Rat – and control strains”, written up in this thesis was conducted at the University of Cape Town, South Africa, 2006/07. The title of Diplombiologe (equ. Master of Science) was awarded by the University of Freiburg, Germany. Download the thesis as PDF here.
Animal models for attention-deficit/hyperactivity disorder (AD/HD) provide valuable insight into the neurophysiology of the disease and serve to test novel treatments. The spontaneously hypertensive rat (SHR) mimics all behavioural characteristics of AD/HD. It is the most widely used and best understood animal model for AD/HD. As an inbred strain, the SHR has a strong genetic disposition for AD/HD-like behaviour. However, the developmental pathology of AD/HD stresses the importance of environmental influences especially during early ages.
This study sought to further characterize the SHR in two different ways: (1) the influence of the early postnatal environment on the expression of AD/HD-like be-haviour was tested in an experiment in which SHR pups were cross-fostered onto dams of the Wistar Kyoto (WKY) and Sprague-Dawley (SD) control strains and tested thirty days after birth (P30) for AD/HD-like behaviour in the open field (OF) and elevated plus maze (EPM) apparatus.
(2) in parallel experiments SHR were tested to mimic a specific aspect of AD/HD in humans, namely its comorbidity with substance abuse disorder (SUD) in adolescence. The susceptibility of SHR to the rewarding effects of ketamine was tested with the conditioned place preference (CPP) paradigm. OF tests were employed to study the behavioural effects of ketamine on SHR, WKY and SD rats. To investigate neural correlates of ketamine-induced behaviour an attempt was made to quantify c-fos expression in the prefrontal cortex and the nucleus accumbens of SHR and control strains. This study showed no effect of cross-fostering on the behaviour of the SHR, confirming its strong genetic determination. At P30 SHR displayed behaviour that was different from both control strains. However at P60, locomotor activity was not different between SHR and SD rats. These findings challenge the notion that SHR is a good model for AD/HD post-puberty. Ketamine was shown to have a differential effect on SHR and WKY. The OF tests revealed a stimulatory effect of ketamine on locomotor behaviour only in the SHR. Ketamine CPP, not shown in rats before, was found in WKY but not in SHR. The prevalence for SUD in AD/HD was not mimicked by SHR.