Browsing Electronic Theses and Dissertations by Subject "5-HT2A"
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ItemINDIVIDUAL DIFFERENCES IN IMPULSIVE ACTION AND TEMPORAL ESTIMATION: INTERACTION WITH THE SEROTONIN (5-HT) 5-HT2A RECEPTORFink, Latham Henry Leeds; Cunningham, Kathryn A; Moeller, F G; Elferink, Cornelis J; Green, Thomas A; Sowers, Lawrence CThe tendency towards patterns of impulsive behaviors and decisions extends across many neuropsychiatric conditions, such as substance use disorders, and leads to problematic consequences which may complicate effective treatment. Impulsivity is a multi-dimensional psychological construct that reflects rapid, premature, inappropriately timed, and/or delay-averse behavior with poor consideration of negative consequences. An important temporal aspect of this construct underlies impulsive behaviors, and high impulsive individuals display differences in cognitive timing abilities (e.g., temporal overestimation). The neurobiological and cognitive factors that lead to impulsivity remain largely unknown, although rodent models of distinct forms of impulsivity, such as impulsive action, have facilitated identification of several neural pathways (e.g., prefrontal cortex, PFC) and neurotransmitter systems (e.g., serotonin, 5-HT) that regulate impulsive action. Manipulation of the 5-HT2A receptor (5-HT2AR) influences impulsive action and timing functions, suggesting that functional capacity of the 5-HT2AR system may drive the predisposition to inherent impulsive action. Few studies have defined the neurobiological determinants of individual differences in impulsive action or behavioral timing, which may be important for directing the development of appropriate pharmacotherapeutics. The present studies were designed to gain insights into the nature and origins of impulsive action and its relationship to temporal representations using rat models. Task manipulations were used to probe the role of behavioral timing in the 1-choice serial reaction time (1-CSRT) task model of impulsive action. Individual differences in impulsive action and behavioral timing were assessed across the 1-CSRT task to the interval bisection task, an additional independent task of explicit timing. The behavioral pharmacology of the 5-HT2AR was systematically evaluated in both tasks to elucidate the role of the 5-HT2AR in mediating temporal aspects of impulsive action. Furthermore, expression and function of the 5-HT2AR in the mPFC was evaluated across individual differences in impulsive action to determine if such individual differences reflect variation of the cortical 5-HT2AR system. Collectively, these studies extend human research into animal models to demonstrate a relationship between impulsivity and timing and provide evidence for the involvement of the 5-HT2AR in mediating this relationship.