No description available.

Thesis (Ph.D)--University of Alberta, 1997. / Submitted to the Faculty of Graduate Studies and Research in partial fulfilment of the requirements for the degree of Doctor of Philosophy, Faculty of Pharmacy and Pharmaceutical Sciences. Also available online.

A larqe body of evidence supports the conclusion that mesolimbic dopaminerqic neurons, in particular those that innervate the nucleus accumbens (n.ACC), are important for the expression of d-amphetamine stimulated locomotor behavior (ASLB) . However, one recent study has contradicted this conclusion, reporting that bilateral lesions of the n.ACC fail to block ASLB. It appears that this study contains a methodoloqical flaw in that it employed a qeneral measure of activity which did not distinquish between locomotion and rcaring. In the present study, we used observer ratinqs of videotaped responses to determine the seperate effects of 2.0 mq/kq d-amphetamine on locomotion and rearinq in rats with either sham or radio-frequency lesions of the n.ACC. It was found that n.ACC lesiongs blocked the locomotor stimulation, but not the increased rearinq, which follows d-amphetamine administration. Additionally, the time spent engaging in stereotyped behaviors followinq administration of a hiqh dose of the donamine agonist apomorphine was not affected by the lesion. These results support the general conclusion that dooaminemic terminals in the n.ACC are important for the expression of ASLB, and further suggest that d-amnhetamine-stimulated locomotion and rearing are mediated throuoh different neural suibstrates.

No description available.

No description available.

Recently, several novel technologies have emerged with substantial benefits in toxicological analysis. These include the development of beadbased multiplex immunoassay (Suspension Bead Array, SBA), the use of reduced-volume centrifugal ion-exchange extraction (SpinSPE), and Ultra-Performance (TM) liquid chromatographic separation coupled to mass spectrometry (UPLC(TM)/MS n ). This work sought to investigate the efficacy and practicality of these innovative approaches against a benchmark of established methods and instrumentation for the screening and confirmation of amphetaminetype substances. This study begins with a statistical survey of amphetaminetype substances encountered in an accredited forensic laboratory supporting the Australian Capital Territory and regional New South Wales. Over the 5year period 2001-2005, it was determined that 6683 case submissions required presumptive screening for amphetamines. Of these cases, 1269 (19.0%) required confirmative analysis of amphetaminetype substances, including amphetamine, methamphetamine, MDA, MDMA, MDEA, ephedrine, pseudoephedrine, and phentermine. Such analytical needs were then used in comparative assessment of the novel and established methodologies, including examination of immunoassay specificity, extraction efficiency, chromatographic resolution, general resource efficiency, and total analysis time. Development of a beadbased immunoassay platform (SBA) for multiplex amphetamines analysis proved to be a complex task. Efforts to multiplex the amphetamine and methamphetamine immunoassay models into a single assay exhibited a significant degree of non-specific antibody cross-reactivity. However, the merits of the individual bead assays were demonstrated. Upon comparison with commercially available enzyme-linked immunosorbent assays for amphetamine or methamphetamine (ELISA), it was observed that the SBA models exhibited specificity comparable to that of the ELISA assays and linearity over a concentration range of toxicological relevance (0-1000 ng/mL amphetamine or methamphetamine). In addition, the results indicated the practical applicability of the individual SBA assays for an oral fluid matrix, and demonstrated significant reductions in the volumes of reagents required and length of time of analysis. Additionally, in an optimised multiplex system, the amount of sample required for screening could be reduced as the SBA technology theoretically permits analysis of up to 100 different drugs or metabolites from one volume of sample. The aspect of forensic sample conservation was further explored with investigation of reduced-volume extraction techniques, such as the application of centrifugal ionexchange extraction columns (SpinSPE). Following initial development, the SpinSPE technique was applied to the isolation of amphetaminetype substances from oral fluid and compared with a mixedmode SPE method for both extraction and resource efficiency. From the observed results, both extraction methods were demonstrated to be effective in the isolation of amphetamine, methamphetamine, ephedrine, pseudoephedrine, PMA, MDA, MDMA, MDEA, MBDB, and 2CB from an oral fluid matrix with detection by heptafluorobutyric acid derivatisation (HFBTA) and GC/MS. The SpinSPE model demonstrated comparable efficacy with reduced sample volume (200 쌩, as well as significant reductions in the volumes of reagents required for column conditioning, washing, and elution. In addition, the linear working range (0-2000 ng/mL) and sensitivity of the method indicated the potential to further reduce sample volume. In the confirmative separation and identification of drug compounds, the technological advancement of UltraPerformance (TM) liquid chromatography (UPLC(TM)) has recently evolved from efforts to improve LC resolution, sensitivity, and time of analysis. In this research, UPLC(TM) coupled to mass spectrometry was demonstrated to be capable of rapidly identifying several amphetaminetype substances (phenylethylamine, amphetamine, phentermine, methamphetamine, ephedrine, pseudoephedrine, PMA, 4MTA, MDA, MDMA, MDEA, MBDB) and ketamine in an analysis time of less than five minutes. In addition, UPLC(TM)/MS demonstrated a resolving power comparable to GC/MS with significantly reduced instrumental analysis time. This research reveals the promise of these new applications in advancing towards a more efficient and modernised systematic toxicological approach. The continued development and optimisation of SBA multiplex immunoassays will permit customisable systems capable of simultaneously detecting numerous compounds with antibodybased sensitivity and selectivity. In circumstances where low sample volumes are required for confirmation of drug use, such as in roadside saliva drug testing for driving under the influence offences, reducedvolume SpinSPE has been demonstrated to be a practical and effective alternative for sample preparation. In addition, a more streamlined procedure is further enhanced with the use of UPLC(TM) coupled to mass spectrometry for analyte separation and molecular identification. It is expected that illicit drug use will remain a significant public concern. With the continued desire for more rapid and comprehensive methodologies, further study of these and other innovative technologies will be of considerable future benefit to laboratories such as that serving the Australian Capital Territory region.

No description available.

Dissertation (Ph.D.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references.

Thesis (Ph.D)--History, Technology and Society, Georgia Institute of Technology, 2010. / Committee Chair: Tone, Andrea; Committee Member: Flamming, Douglas; Committee Member: Krige, John; Committee Member: Metzl, Jonathan; Committee Member: Usselman, Steven. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph. D.)--University of Chicago, Dept. of Psychology (Biopsychology), Dec. 2002. / Includes bibliographical references. Also available on the Internet.