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Dopamine Release Dynamics Change during Adolescence and after Voluntary Alcohol Intake
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2014 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 5, e96337- p.Article in journal (Refereed) Published
Abstract [en]

Adolescence is associated with high impulsivity and risk taking, making adolescent individuals more inclined to use drugs. Early drug use is correlated to increased risk for substance use disorders later in life but the neurobiological basis is unclear. The brain undergoes extensive development during adolescence and disturbances at this time are hypothesized to contribute to increased vulnerability. The transition from controlled to compulsive drug use and addiction involve long-lasting changes in neural networks including a shift from the nucleus accumbens, mediating acute reinforcing effects, to recruitment of the dorsal striatum and habit formation. This study aimed to test the hypothesis of increased dopamine release after a pharmacological challenge in adolescent rats. Potassium-evoked dopamine release and uptake was investigated using chronoamperometric dopamine recordings in combination with a challenge by amphetamine in early and late adolescent rats and in adult rats. In addition, the consequences of voluntary alcohol intake during adolescence on these effects were investigated. The data show a gradual increase of evoked dopamine release with age, supporting previous studies suggesting that the pool of releasable dopamine increases with age. In contrast, a gradual decrease in evoked release with age was seen in response to amphetamine, supporting a proportionally larger storage pool of dopamine in younger animals. Dopamine measures after voluntary alcohol intake resulted in lower release amplitudes in response to potassium-chloride, indicating that alcohol affects the releasable pool of dopamine and this may have implications for vulnerability to addiction and other psychiatric diagnoses involving dopamine in the dorsal striatum.

Place, publisher, year, edition, pages
2014. Vol. 9, no 5, e96337- p.
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-227196DOI: 10.1371/journal.pone.0096337ISI: 000335510600094OAI: oai:DiVA.org:uu-227196DiVA: diva2:729810
Available from: 2014-06-26 Created: 2014-06-24 Last updated: 2015-01-22Bibliographically approved
In thesis
1. Early Environment, Adolescent Alcohol Drinking and Neurobiological Responses to Drugs
Open this publication in new window or tab >>Early Environment, Adolescent Alcohol Drinking and Neurobiological Responses to Drugs
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genes and environment interact to determine an individual’s vulnerability or resilience to several psychiatric disorders, including alcohol use disorder (AUD). Alcohol use is often initiated during adolescence and early onset drinking is associated with increased risk for later AUD. Childhood and adolescence are periods of extensive brain maturation, which makes young individuals more susceptible to environmental influence. However, little is known about early environmental influence on reward pathways and behaviors involved in the development of AUD. Changes in the endogenous opioid and dopamine systems, as well as individual differences in risk behaviors are all believed to play important roles in the increased vulnerability seen after adverse early life events and early onset drinking. The overall aim of the thesis was therefore to investigate the influence of early environmental factors on adolescent alcohol intake, endogenous opioids, dopamine dynamics and alcohol-induced effects in rats to increase our knowledge of neurobiological factors underlying vulnerability to AUD. Furthermore, individual behavioral differences and their correlation to basal and drug-induced neurobiological responses in rats were also investigated. Animal models of different early environments, e.g. maternal separation and social vs. single housing, and adolescent alcohol consumption have been used to study effects on behavior, endogenous opioid peptides and dopamine dynamics. The results identified the amygdala and dorsal striatum as interesting brain regions in which endogenous opioids and dopamine, respectively, are impacted by early environmental factors. The amygdala and the dorsal striatum are both hypothesized to be involved in the shift from initial drug use to compulsive use and changes in these areas may be underlying environmentally increased vulnerability to AUD. Furthermore, behavioral phenotypes in relation to individual neurobiological responses were identified. High risk-taking behavior was associated with a more pronounced response to amphetamine, but the inherent dopamine response was instead associated with risk-assessment behavior. In conclusion, several brain regions of interest for future research were identified. Furthermore, the results contribute to increased understanding of factors involved in the development of vulnerability for AUD in adolescents and young adults.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 99 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 190
adolescence, beta-endorphin, dopamine, dynorphin, endogenous opioids, enkephalin, high-speed chronoamperometry, housing conditions, maternal separation, multivariate concentric square field™ test, open field test, radioimmunoassay, voluntary alcohol intake, Wistar rats
National Category
Neurosciences Pharmacology and Toxicology
Research subject
Pharmaceutical Science
urn:nbn:se:uu:diva-229992 (URN)978-91-554-9011-9 (ISBN)
Public defence
2014-10-10, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2014-09-19 Created: 2014-08-18 Last updated: 2015-01-22

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