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Serotonin and disorders of human disinhibition : alcohol abuse and dependence, aggression and impulsivity

A wealth of data supports the hypothesis that the neurotransmitter serotonin regulates the intake of ethanol, and is involved in the development of alcoholism in humans. Reduced functioning of the serotonergic system hypothetically increases alcohol intake in both animals and humans. In this thesis, it was proposed that the effect of lowered serotonergic function on alcohol intake is mediated by an increase in disinhibition. The hypothesis that lowered serotonin increases disinhibition was tested in separate groups of individuals at high risk for the development of psychopathology: nonalcoholic young men with a strong family history of paternal alcoholism, and adolescent men with previous histories of physically aggressive behavior. Lowered serotonergic synthesis (and thus presumably function) was experimentally induced through a transient dietary reduction in the availability of the amino add precursor of serotonin, tryptophan. Disinhibition was quantified using a go/no-go task previously shown to characterize psychopaths and children with attention deficit hyperactivity disorder as disinhibited. In the first study, acute tryptophan depletion had no effect on aggressive responding on a modified competitive reaction time aggression task, but increased disinhibition in young men at risk for alcoholism. This effect was independent of the tryptophan depletion-induced mood alterations. The effect tryptophan depletion on disinhibition was not replicated in the second study with previously aggressive adolescent men. A number of explanations for this were posited, including the presence of a ceiling effect. An association between disinhibition and executive functioning (cognitive abilities associated with proper functioning of the prefrontal cortex, such as working memory, planning abilities) was demonstrated in the second study. In a third preliminary study, no association between disinhibition on the go/no-go task and allelic polymorphisms of the dopamine D4 receptor

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34998
Date January 1997
CreatorsLeMarquand, David Gordon, 1966-
ContributorsPihl, Robert O. (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Department of Psychology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001616585, proquestno: NQ44490, Theses scanned by UMI/ProQuest.

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