Petrus Karel The role of serotonin transporter genetic variation in the cause and cure of cocaine addiction
Serotonin is an important substance in the brain that regulates many processes and the extracellular concentration of serotonin is determined by the serotonin transporter (5-HTT). People with a lower production of 5-HTT are more likely to develop an addiction.read more
Petrus Karel The role of serotonin transporter genetic variation in the cause and cure of cocaine addictionSerotonin is an important substance in the brain that regulates many processes and the extracellular concentration of serotonin is determined by the serotonin transporter (5-HTT). People with a lower production of 5-HTT are more likely to develop an addiction. We also know that when we mimic this genetic variance in rats by means of a "knock-out model" (which every "knockout rat" does not have 5-HTT at all) these rats are also more susceptible to addiction. In this thesis we used knockout rats to find out why these animals are more susceptible to the development of addiction and we have tried to treat addicted animals. We have compared the brain of these "knockout" rats with those of control "wildtype" rats using MRI. We showed there are differences in the in brain structure of both addicted and non-addicted groups of "knockout" and "wild-type rats".
Previous research has shown that the variation of 5-HTT does not only have disadvantages. For instance, these animals are better processing new information and may be more sensitive to pharmacological intervention. In the second half of the thesis we tested two possible treatments for addiction: 1) pharmacological intervention by D-cycloserine and 2) a behavioral intervention called "counter-conditioning". The outcome of these two studies was similar: both pharmacological and behavioral therapy worked well in the "wild-type" rats, but had limited to no effect in the 5-HTT "knockout" rats.
Date, time and location PhD defense
- Date: 26 October 2018
- Time: 10.30 hrs
- Location: Radboud Universiteit, Academiezaal Aula, Comeniuslaan 2
Peter Karel was born in Waalre, on August 27th, 1988. After secondary school at the Philips van Horne SG in Weert, he obtained his bachelor and later his research master Biomedical Sciences at the Radboudumc in Nijmegen. During this period he became highly interested in Neuroscience. As part of the master program he worked as a research student for 6 months at the department of Neuroscience of the Radboudumc, studying cognitive fear extinction and cognitive flexibility in the serotonin transporter knockout rat (under supervision of Dr. L. Nonkes and Dr. J.R. Homberg). Additionally, during the second year he investigated the role of several micro RNAs in the development of autism spectrum disorders caused by maternal valproic acid use during pregnancy (under supervision of Dr. A. Aschrafi and Dr. J.R. Homberg. In 2011 he obtained his Master of Science degree with honors and was offered a PhD in the group of Dr. J.R. Homberg that led to this dissertation.
- Promotor(s): Prof. L. Reneman and dr. J.R. Homberg
- Co-promotor(s): M.M.M. Verheij PhD