Research into factors that determine the propensity to self-administer cocaine has shown that stressors can determine the amount of cocaine self-administered as well as the rate of acquisition. However, the interaction between the genetic make-up of the animal and stress is unknown. This study investigated this interaction by using the genetic animal model consisting of apomorphine susceptible (APO-SUS) and unsusceptible (APO-UNSUS) rats. Animals were allowed to self-administer 0.25 mg/kg cocaine under stressful and habituated conditions. This study revealed that the amount of cocaine consumed was highly dependent on the genetic make-up of the animal as well as the amount of stress during self-administration. Under habituated circumstances the APO-UNSUS rats took far more cocaine than the APO-SUS rats. Under stressful circumstances, however, the APO-SUS rats took far more cocaine than the APO-UNSUS rats. This difference in the amount consumed by APO-SUS and APO-UNSUS rats is likely to be due to the specific neurobiological features of their dopaminergic and, possibly, noradrenergic system as well as the reactivity of their HPA-axis. It is suggested that the amount of a drug consumed and, accordingly, its addictive potential and 'drug-vulnerability' are determined by the interaction between the genetic make-up of the animals and stress, and not by either component alone.
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http://dx.doi.org/10.1016/j.neuropharm.2004.12.014 | DOI Listing |
Sci Rep
September 2016
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22.
View Article and Find Full Text PDFFront Behav Neurosci
August 2014
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen, Netherlands.
Schizophrenia is a complex mental disorder caused by an interplay between genetic and environmental factors, including early postnatal stressors. To explore this issue, we use two rat lines, apomorphine-susceptible (APO-SUS) rats that display schizophrenia-relevant features and their phenotypic counterpart, apomorphine-unsusceptible (APO-UNSUS) rats. These rat lines differ not only in their gnawing response to apomorphine, but also in their behavioral response to novelty (APO-SUS: high, APO-UNSUS: low).
View Article and Find Full Text PDFPhysiol Behav
February 2011
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience & Nijmegen Centre for Molecular Life Sciences (NCMLS), Faculty of Science, Radboud University Nijmegen, 6525 GA, Nijmegen, The Netherlands.
A synergistic relationship is thought to exist between hypothalamic-pituitary-adrenal (HPA) axis activity and dopamine neurotransmission. To test whether a high response to dopamine indeed implies a hyperactive HPA-axis, we here used Wistar rats that were selected twice independently (original and replicate lines) for a high or low susceptibility to the dopamine receptor agonist apomorphine (so-called APO-SUS and APO-UNSUS rats, respectively). The APO-SUS rats from the original line displayed a hyperactive HPA-axis in that higher basal and stress-induced adrenocorticotropic hormone (ACTH) levels, and lower basal free-corticosterone levels were observed than those found in the original APO-UNSUS rats.
View Article and Find Full Text PDFBehav Brain Res
March 2010
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour & Nijmegen Centre for Molecular Life Sciences, Faculty of Science, Radboud University Nijmegen, RT282, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
Animal models allow insights into complex neurodevelopmental disorders. Apomorphine-susceptible rats (so-called APO-SUS rats) provide a model that displays a complex phenotype with schizophrenia-related features and together with its phenotypic counterpart (APO-UNSUS rats) has been independently generated twice (original and replicate rat lines). To understand the molecular basis underlying this phenotype, we here performed mRNA expression profiling in various APO-SUS and APO-UNSUS rat brain regions.
View Article and Find Full Text PDFBehav Genet
September 2007
Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences (NCMLS) & Institute for Neuroscience, Faculty of Science, Radboud University Nijmegen, 282 RT, Geert Grooteplein Zuid 28, Nijmegen, 6525 GA, The Netherlands.
A combination of genetic variations, epimutations and environmental factors may be involved in the etiology of complex neurodevelopmental disorders like schizophrenia. To study such disorders, we use apomorphine-unsusceptible (APO-UNSUS) Wistar rats and their phenotypic counterpart apomorphine-susceptible (APO-SUS) rats that display a complex phenotype remarkably similar to that of schizophrenic patients. As the molecular basis of the APO-SUS/UNSUS rat model, we recently identified a genomic rearrangement of the Aph-1b gene.
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