Individual sensitivity to novelty and (+)-3,4-methylenedioxymethamphetamine: Roles for serotonin and GABA neurotransmission

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Individual sensitivity to novelty and (+)-3,4-methylenedioxymethamphetamine: Roles for serotonin and GABA neurotransmission

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dc.contributor.advisor Kathryn A. Cunningham en_US
dc.creator Julie Danielle Ross en_US
dc.date.accessioned 2011-12-20T16:04:39Z
dc.date.available 2010-09-28 en_US
dc.date.available 2011-12-20T16:04:39Z
dc.date.created 2006-04-27 en_US
dc.date.issued 2005-01-27 en_US
dc.identifier.other etd-04272006-105627 en_US
dc.identifier.uri http://hdl.handle.net/2152.3/103
dc.description.abstract Drug addiction continues to be a problem in our society, and better understanding of the neuroanatomical and neurochemical alterations that delineate the switch between causal drug use and compulsive drug addiction is needed. Characterizing what makes one individual more vulnerable to the development of compulsive drug-taking behaviors may hold the key to this complex phenomenon. Because individual differences in humans exist to the subjective effects of 3,4-methylenedioxymethamphetamine (MDMA) and these differences are rooted, in part, in individual sensitivity to the drug effects, we utilized two animal models of increased sensitivity in the current studies. First, in a sensitization animal model we examined the mechanisms of increased sensitivity to (+)-MDMA and found a critical role for serotonin (5-HT) neurotransmission, in particular the 5-HT2A receptor (5-HT2AR) in the nucleus accumbens (NAc) and prefrontal cortex (PFC). We then carried this finding into a model of individual difference in which animals are separated based on their differential locomotor response to a novel environment into high responder rats (HR) and low responder rats (LR). In addition to an increased sensitivity to (+)-MDMA, we uncovered basal differences in the 5-HT system between HR and LR rats, an increased level of expression of the 5-HT2AR in the NAc of HR rats in particular. Additionally, we examined the brain structures activated secondary to novelty in HR vs. LR rats and the phenotype-specific behavioral changes after repeated exposure to the environment. Our findings revealed a strong influence of GABA neurotransmission that may underlie the differences between HR vs. LR behavioral phenotypes. These findings lend support to the idea that the neural systems underlying drug-induced and stress-induced behaviors overlap and may help to understand how individual sensitivity to both (+)-MDMA and novelty may confer an increased vulnerability to the development of compulsive drug-taking behavior. en_US
dc.format.medium electronic en_US
dc.language.iso eng en_US
dc.rights Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. en_US
dc.subject vulnerability en_US
dc.subject MDMA en_US
dc.subject drug abuse en_US
dc.subject DOI en_US
dc.subject c-Fos en_US
dc.subject 5-HT2A receptor en_US
dc.title Individual sensitivity to novelty and (+)-3,4-methylenedioxymethamphetamine: Roles for serotonin and GABA neurotransmission en_US
dc.type.material text en_US
dc.type.genre dissertation en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Neuroscience en_US
dc.contributor.committeeMember Thomas A. Kent en_US
dc.contributor.committeeMember Terry E. Robinson en_US
dc.contributor.committeeMember Mary L. Thomas en_US
dc.contributor.committeeMember Cheryl S. Watson en_US

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