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Identifier 000454777
Title Ο ρόλος της σωματικής άσκησης στα νευρωνικά κυκλώματα ανταμοιβής : πειραματική μελέτη σε επίμυες
Alternative Title Interactions between physical exercise and neural reward systems : an experimental study in rats
Author Κατσιδώνη, Βασιλεία-Χρυσοβαλάντη
Thesis advisor Παναγής Γεώργιος
Reviewer Καστελάκης Ανδρέας
Θερμού Κυριακή
Αντωνίου Αικατερίνη
Πιτσίκας Νικόλαος
Σιδηροπούλου Κυριακή
Σταματάκης Αντώνιος
Abstract According to the diathesis-stress model, environmental stimuli interact with genetic predisposition resulting in the development of a psychiatric disorder, including addiction, which is defined as a brain disorder characterized by craving and loss of control despite the negative effects. It is well-known that the mesolimbic dopaminergic system plays the main role in addiction. Adolescence is considered as a period during which a majority of structural and functional changes are taking place, while the dysfunctional brain development is associated with increased risk of adopting high risk behaviors such as drug use and abuse. It seems that interventions targeting an individual’s physiology by activating the central nervous system, i.e physical activity, mostly promote health and wellness. Research data indicate that physical activity is a natural reinforcer that exerts antidepressant and anxiolytic effects which have been negatively associated with the use of addictive, psychotropic substances. Recently, researchers have focused their attention on the effects of physical activity on the prevention or treatment of addicted individuals. However, little is known about the effects of exercise on neural reward circuit, specifically during adolescence. Given that human brain is not fully mature during adolescence, the effects of any entrenched behavior appear more robust. At the preclinical level, animal models for exercise include treadmill and voluntary wheel-running. It has been proven that chronic voluntary exercise simulates human behavior. A question that still remains unanswered is whether exercise may modify neural reward circuits, during brain development, via long-term and permanent neuroadaptive changes and subsequently contribute decisively to the substance use. Therefore, the purpose of the present PhD thesis was to study the effects of chronic voluntary exercise during development (from weaning until early adulthood), and on the sensitivity of neural reward system. Four studies were performed. In our first study we used the intracranial self-stimulation (ICSS) paradigm in order to compare the sensitivity of reward system of lateral hypothalamus between exercised and sedentary group according to the following parameters: (a) the time required for the acquisition of the lever- pressing, (b) the minimum frequency required for the acquisition of the self- stimulation behavior, (c) total number of primings until the acquisition of the self-stimulation behavior, (d) the ICSS threshold and asymptote after the stabilization of the self- stimulation behavior. Subsequently, we examined the effect of different doses of cocaine, morphine and Δ9-THC on the efficacy of brain stimulation reward. In our second study, we examined the effect of chronic voluntary exercise on spontaneous locomotor activity of laboratory rats, after the exposition to a novel environment, which is positively associated with increased vulnerability in drug- seeking behavior. Afterwards, we examined the effect of different doses of cocaine, morphine and Δ9-THC on locomotor activity. In our third study, we examined the effect of chronic voluntary exercise on the basal levels of dopamine and its metabolites in the striatum, a structure that is known for its implication on the reward and addiction processes. Moreover, we compared the levels of dopamine and its metabolites between exercised and sedentary group after the injection of cocaine, morphine and Δ9-THC. Lastly, in our fourth study, we examined the levels of D2 receptors in the brain reward regions of VTA, nucleus accumbens and prefrontal cortex. Our findings showed that chronic voluntary exercise decreased the sensitivity of neural reward circuits in laboratory animals as well as the exploratory behavior on a novel environment. As shown in the neurochemical study, these effects could be explained by the decreased dopaminergic activity in the striatum. Regarding the psychostimulants, exercise decreased the reward- facilitating effect of cocaine in the ICSS procedure; however, it did not diminish the effect of cocaine on locomotion. The decreased dopaminergic activity in the striatum of exercised rats may explain the protective effect on the rewarding effect of cocaine, although it does not explain the increased hyperlocomotion. Regarding the opioids, exercise increased the reward- facilitating effect of morphine in the ICSS procedure, while it decreased the locomotor activity. The increased dopaminergic activity in the striatum of exercised rats may explain the above-mentioned results. Regarding the cannabinoids, exercise inhibited the biphasic effects of Δ9-THC on the reward (hedonic effect at the low dose and anhedonic effect at the high dose), as well as the effect on the locomotor activity. Furthermore, the dopaminergic activity in the striatum was attenuated after the injection of the low dose of Δ9-THC. This finding could explain the inhibition of the rewarding effect and the hyperlocomotion at the behavioral level. The autoradiography study did not show statistically significant differences of D2 receptor levels in the region of VTA, nucleus accumbens or prefrontal cortex. The present PhD thesis offers new insights, at the preclinical level, that reinforce the idea that physical exercise could prevent drug use and abuse by modifying the neural reward circuits during development and especially during adolescence. Moreover, our results confirm the protective effect of chronic voluntary exercise on the euphoric effects of psychostimulants and cannabinoids by association with striatal dopaminergic levels.
Language Greek
Subject Autoradiography
Locomotor activity
Physical exercise
Ενδοκρανιακός αυτοερεθισμός
Κινητική δραστηριότητα
Issue date 2022-01-24
Collection   School/Department--School of Social Sciences--Department of Psychology--Doctoral theses
  Type of Work--Doctoral theses
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