1,721,239 research outputs found
The retrorubral nucleus: a study on consequences of its dysfunction in cats. Implications for its contribution to symptoms seen in Parkinson's disease
No full textItem does not contain fulltextkun, 17 maart 1998Promotor : Cools, A.R
Corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus: Morphological and functional aspects
No full textItem does not contain fulltextK.U. Nijmegen, 14 mei 1997Promotores : Cools, A.R., Meek, J.129 p
Gating of auditory evoked potentials and prepulse inhibition: an animal modeling approach. Distinct rodent genotypes and the role of dopamine
No full textItem does not contain fulltextKUN, 28 mei 2001Promotores : Cools, A.R., Coenen, A.M.L
Individual differences in the release of newly-synthesised and previously stored accumbal dopamine: a rodent study in low and high responders to novelty.
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80214.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 08 april 2009Promotor : Cools, A.R.269 p
Upper motor neuron death in ALS. Mechanistic studies in an in vitro model
No full textItem does not contain fulltextKUN, 07 mei 2002Promotores : Bär, P.R., Cools, A.R. Co-promotor : Joosten, E.A.J
Phenotyping the serotonin transporter knockout rat: a behavioural, pharmacological and physiological approach. A new animal model of human serotonergic disorders.
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65625_phenthset.pdf (Publisher’s version ) (Open Access)
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71034.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 27 november 2008Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
Factors contributing to the intake of alcohol and cocaine by rats: Role of genetic background, early-life events and stressors.
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27385.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 08 februari 2006Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.163 p
Neurobiological mechanisms underlying individual differences in responses to addictive drugs in rats: with special focus on dopamine.
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51889.pdf (Publisher’s version ) (Open Access)This thesis addresses the intriguing question why some individuals easily become addicted to drugs, while others do not. A key player in this phenomenon is the neurotransmitter dopamine. Several studies have indicated that there are differences in the dopaminergic system of rats that are more or less prone to addiction. In this thesis we describe neurobiological differences in the dopaminergic system of the so-called apomorphine-susceptibe (APO-SUS) and unsusceptible (APO-UNSUS) rats. These rats have a different vulnerability to the dopamine D2 agonist apomorphine and show behavioural, physiological, endocrinological and genetical differences. Most importantly, they show a difference in drug self-administration (alcohol, cocaine) and drug sensitivity. The aim of this thesis was to investigate the neurobiological differences between these two rat lines that might underlie their difference in drug sensitivity. Thus, two types of research were conducted. First, the dopaminergic system was investigated using in vivo microdialysis, measuring extracellular levels of dopamine, and in vitro immunocytochemistry for the enzyme tyrosine hydroxylase (TH), which is the rate-limiting enzyme in dopamine synthesis. Second, the response of the dopaminergic system to in vivo administration of amphetamine and cocaine was investigated with prepulse inhibition as read-out parameter. The main finding of these studies was that there are pronounced differences in the basic structure of the dopaminergic system between APO-SUS and APO-UNSUS rats. In addition, the response of their dopaminergic system to environmental and drug challenges was different. Finally, the underlying cellular mechanism that mediates the response to amphetamine was also different between the rat lines. In conclusion, individuals that have a different drug sensitivity have a different make-up of the dopaminergic system and this system also responds differently to environmental and drug challenges. Thus, addiction has a clear neurobiological basis that awaits further investigation in order to understand the mechanisms underlying individual differences in drug sensitivity.RU Radboud Universiteit Nijmegen, 10 januari 2007Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
Molecular understanding of a rat model with schizophrenia-related features. Gene-dosage imbalance of the gamma-secretase component Aph-1b in APO-SUS and -UNSUS rats
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30145.pdf (Publisher’s version ) (Open Access)Wistar rats pharmacogenetically selected for a high susceptibility to the dopamine agonist apomorphine (APO-SUS rats) display many differences with their phenotypic counterpart (APO-UNSUS rats), which are remarkably similar to those observed in schizophrenic patients. In this thesis we tried to understand the molecular mechanism underlying the APO-SUS/-UNSUS complex phenotype, which might aid in finding the cause of schizophrenia in human. Microarray expression analyses revealed in APO-SUS rats, relative to -UNSUS rats, a reduced expression of Aph-1b, a component of the gamma-secretase enzyme complex that is involved in multiple (neuro)developmental signalling pathways. These differences were caused by different gene copy numbers; APO-SUS rats harbour only one or two gene copies of Aph-1b, whereas APO-UNSUS rats contain three copies. This gene-dosage imbalance was caused by an unequal crossing-over event involving a segmental duplication within the Aph-1b locus. Although the expression levels of the other gamma-secretase components were not different, the gamma-secretase cleavage activity towards several substrates was affected and the Aph-1b genotypes segregated with a number of behavioural phenotypes. Through crossing and genetic re-selection, new rat lines were generated with one, two or three Aph-1b gene copies against otherwise similar genetic backgrounds. These rats revealed, next to affected Aph-1b expression levels throughout development, temporal, tissue- and substrate-specific changes in gamma-secretase cleavage activity. Preliminary studies on transgenic Xenopus laevis expressing Aph-1a under control of the proopiomelanocortin promoter, imply that the manipulation of Aph-1 expression in Xenopus melanotrope cells leads to a modified sensitivity of the dopaminergic system. In conclusion, these studies suggest that a subtle change in the expression of a (neuro)developmentally important protein may spatio-temporally affect diverse signalling pathways, ultimately resulting in a complex phenotype that is generally thought to be caused by multiple affected genes. Furthermore, we implicate the possible involvement of the gamma-secretase enzyme in complex disorders, like schizophrenia.RU Radboud Universiteit Nijmegen, 22 december 2006Promotores : Martens, G.J.M., Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
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