>Magister Scientiae - MSc / Methamphetamine (MA), also known as ‘Tik’, has detrimental short- and long-term psychological and morphological effects on the central nervous system (CNS). The lipophilic nature of MA allows it to cross the blood-brain barrier (BBB) which normally plays a protective role in limiting solute exchange (including narcotics) into the neuronal tissue. Numerous studies have indicated that MA not only crosses the BBB but is implicated in distorting its crucial role in that it increases the permeability of the endothelial cells and thereby compromises its core homeostatic function. The speculated mechanism by which MA elicits its effects involves elevated ROS production which may be reversed by antioxidant treatment. Rooibos herbal tea (Aspalathus linearis) which is well documented for its antioxidative properties and ROS scavenging abilities may therefore be the ideal candidate to reverse the harmful ROS-induced effects of MA. The aim of the study was to investigate the in vitro ameliorating potential of fermented rooibos (Rf) against the MA-induced effects on mouse brain endothelial (bEnd5) cells by utilizing various assays (trypan blue exclusion and XTT viability assays) and physiological parameters (cell numbers, viability, monolayer permeability and cell cycle phases) over a period of 96 hrs. Statistical analysis was performed using the Wilcoxon rank sum test with P<0.05 denoted as significant. Once-off exposure to physiological MA concentrations and Rf resulted in % viability similar to controls by 96 hrs with suppression observed only when the cells were exposed to daily MA (0.1-1000 μM) (P≤0.0063). Exposure to supraphysiological concentrations (≥100 μM) of MA greatly suppressed viability (P≤0.0463). Both daily and once-off treatment to the combinations initially resulted in increased viability however by 96 hrs was similar to- or exceeding the controls (P≤0.0180). MA exposure also resulted in decreased live cell numbers (P≤0.0339) with no effect when exposed to Rf by 96 hrs. The combinations resulted in cell numbers comparable to controls. Dose-dependent increases in electrical resistance were observed in response to singular MA and Rf treatment with lower MA concentrations displaying significant decreases (P≤0.0064). Similar trends were observed with combinations however greater resistance was observed. Increased G1-phase populations (P≤0.0495) in response to singular MA and Rf exposure was noted followed by decreased S-phase fractions (P≤0.0356). While MA decreased G2-M phase cells (P≤0.0498) it was unaffected by Rf. In contrast, the combination of MA and Rf decreased events in the G1-phase (P≤0.0483), with an increased S-phase population (P≤0.0415). In conclusion, the single compounds displayed mirroring effects, decreasing the cells’ permeability and causing G1-phase arrest. The modulatory effects of Rf in combination with MA was illustrated with the restoration of viability and live cell numbers comparable to that of controls, and a more restrictive monolayer as well as reversal of the G1-phase arrest. Findings suggest that Rf may reverse the adverse effects of MA on the BBB.

by Josephine Wing Sze Lau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 84-112). / Abstracts in English and Chinese. / Acknowledgment --- p.iii / Abstract --- p.iv / List of Abbreviations --- p.viii / Chapter CHAPTER ONE: --- INTRODUCTION / Chapter 1.1 --- Methamphetamine (METH) --- p.1 / Chapter 1.1.1 --- Historical Background and Epidemiology --- p.1 / Chapter 1.1.2 --- Physical Effects of METH --- p.4 / Chapter 1.1.3 --- Neurochemical Alternation of METH --- p.6 / Chapter 1.2 --- Mechanisms of METH Toxicity / Chapter 1.2.1 --- Oxidative Stress --- p.8 / Chapter 1.2.1.1 --- Superoxide (O2-) and Superoxide Dismutase (SOD) --- p.10 / Chapter 1.2.1.2 --- "Hydrogen Peroxide (H202), Catalase and Glutathione (GSH)" --- p.11 / Chapter 1.2.1.3 --- Hydroxyl Radical (OH.) --- p.12 / Chapter 1.2.1.4 --- Nitric Oxide (NO) --- p.13 / Chapter 1.2.2 --- Apoptosis --- p.16 / Chapter 1.2.3 --- Excitotoxicity --- p.17 / Chapter 1.2.4 --- Mitochondrial Dysfunction --- p.18 / Chapter 1.2.5 --- Hyperthermia --- p.21 / Chapter 1.2.5.1 --- Cyclooxygenase-2 (COX-2) --- p.23 / Chapter 1.2.5.2 --- Heme-oxygenase-1 (HO-1) --- p.25 / Chapter 1.2.5.3 --- The Effects of Nitric Oxide (NO) on COX-2 and HO-1 Expressions --- p.27 / Chapter 1.3 --- Astrocytes / Chapter 1.3.1 --- Characteristics of Astrocytes --- p.29 / Chapter 1.3.2 --- Astrocyte Functions --- p.30 / Chapter 1.3.3 --- The Role of Astrocytes in METH-induced Neurotoxicity --- p.34 / Chapter 1.4 --- Aim of Project --- p.37 / Chapter CHAPTER TWO: --- MATERIALS AND METHODS / Chapter 2.1 --- Cell Cultures / Chapter 2.1.1 --- Astrocyte Cultures --- p.42 / Chapter 2.1.2 --- CATH.a Cell line and Astrocytes Co-cultures --- p.43 / Chapter 2.2 --- Treatment / Chapter 2.2.1 --- METH Treatment --- p.44 / Chapter 2.2.2 --- Inhibition of Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS) --- p.44 / Chapter 2.3 --- Lactate Dehydrogenase (LDH) Assay --- p.45 / Chapter 2.4 --- Assay for Reactive Oxygen Species (ROS) Formation --- p.47 / Chapter 2.5 --- Assay for Adenosine Triphosphate (ATP) Content --- p.48 / Chapter 2.6 --- Determination of Mitochondrial Membrane Potential (Δ Ψm) --- p.50 / Chapter 2.7 --- Determination of Nitrite Levels in Cultured Astrocytes --- p.51 / Chapter 2.8 --- Western Blot Analysis --- p.52 / Chapter 2.8.1 --- COX-2 --- p.53 / Chapter 2.8.2 --- HO-1 --- p.53 / Chapter 2.9 --- Viability Assay of CATH.a-Astrocyte Cocultures --- p.54 / Chapter 2.10 --- Statistics --- p.55 / Chapter CHAPTER THREE: --- RESULTS / Chapter 3.1 --- The Effects of METH Treatment on Cultured Astrocytes / Chapter 3.1.1 --- Lactate Dehydrogenase (LDH) Activities --- p.56 / Chapter 3.1.2 --- Morphological Changes --- p.56 / Chapter 3.1.3 --- The Production of Reactive Oxygen Species / Chapter 3.1.3.1 --- Rate of change (0-120 min) --- p.57 / Chapter 3.1.3.2 --- Time course (0 - 48 h) --- p.57 / Chapter 3.1.4 --- Change in ATP Content --- p.58 / Chapter 3.1.5 --- Change in Mitochondrial Membrane Potential (Δ Ψm) --- p.59 / Chapter 3.1.6 --- Nitrite levels after METH treatment / Chapter a) --- Striatal astrocytes --- p.59 / Chapter b) --- Mesencephalic astrocytes --- p.60 / Chapter c) --- Cortical astrocytes --- p.60 / Chapter 3.1.7 --- The Effects of Aminoguanidine (AG) on Nitrite Levels / Chapter a) --- Striatal astrocytes --- p.61 / Chapter b) --- Mesencephalic astrocytes --- p.62 / Chapter c) --- Cortical astrocytes --- p.62 / Chapter 3.1.8 --- The Effects of Indomethacin (INDO) on Nitrite Levels / Chapter a) --- Striatal astrocytes --- p.63 / Chapter b) --- Mesencephalic astrocytes --- p.64 / Chapter c) --- Cortical astrocytes --- p.64 / Chapter 3.1.9 --- Change in Cyclooxygenase-2 (COX-2) Protein Levels / Chapter a) --- Striatal astrocytes --- p.65 / Chapter b) --- Mesencephalic astrocytes --- p.65 / Chapter c) --- Cortical astrocytes --- p.66 / Chapter 3.1.10 --- Change in Heme-oxygenase-1 (HO-1) Protein Levels / Chapter a) --- Striatal astrocytes --- p.66 / Chapter b) --- Mesencephalic astrocytes --- p.66 / Chapter c) --- Cortical astrocytes --- p.67 / Chapter 3.2 --- Cell Viability on CATH.a-Astrocyte Cocultures After METH Treatment --- p.67 / Chapter CHAPTER FOUR: --- DISCUSSION AND CONCLUSION --- p.69 / REFERENCES --- p.84

Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic system in the brain, originating in the ventral tegmental area and terminating in the nucleus accumbens, has been shown to be central to the neurobiology of addiction and the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. This common pathway has supported theories suggesting addiction as a case of maladaptive associative learning. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been seen to play a vital role. Vasopressin exerts a long- term facilitatory effect on learning and memory processes. Studies have shown that the stress responsive AVP V1b receptor systems are a critical component of the neural circuitry underlying emotional consequences of drug reward. Oxytocin, on the other hand, has an effect on learning and memory opposite to that of vasopressin. Previous studies have shown that oxytocin caused a decrease in heroin self-administration, as well as attenuated the appearance of cocaine-induced hyperactivity and stereotyped behaviour. Therefore, we adopted a reinstatement conditioned place preference model to investigate whether a V1b antagonist or oxytocin treatment would cause a decrease in methamphetamine seeking behaviour. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in preference was not seen after vasopressin administration in the extinction phase. On the other hand, the change in place preference was enhanced during the reinstatement phase in the animals treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Results showed that rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference behaviour in rats and that this change may be partially restored by vasopressin antagonism, but exaggerated by oxytocin. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Westville, 2012.

Magister Chirurgiae Dentium - MChD / The aim of the study was to document the oral health status of individuals using methamphetamine. Methamphetamine (TIK) is a highly addictive drug that acts as a stimulant for the central nervous system. The clinical picture of methamphetamine abuse is termed “Meth Mouth” and can be explained by contributing factors such as dry mouth, a poor appetite, consumption of large amounts of soft drinks and poor oral hygiene. A cross-sectional study was conducted at 22 different substance addiction treatment centres in the Western Cape. A questionnaire was administered to elicit demographic details, diet, drug addiction, dental status and medical history. The aim of the study was to document the oral health status of methamphetamine users. The study consisted of a convenience sample of 308 participants who used methamphetamine as a primary drug of choice. An oral examination was performed to measure dental caries status (DMFT) and treatment needs. The majority was male, unemployed and between 25 and 29 years old. The mean duration of drug addiction was 6 years predominantly on a daily basis and 93.51% by smoking the drug. The mean DMFT was 10 and dental extractions were the most common procedure performed at the last dental visit. A significant difference was observed between levels of education and the mean number of extractions that were required per participant. The duration of exposure to methamphetamine was related to the number of decayed, missing and filled teeth. The majority experienced a bad taste, stiff facial muscles and a dry mouth when using the drug. Diet included large quantities of liquids (mainly beer and soft drinks) and the majority reported having a poor appetite. Users brushed their teeth less frequently when using methamphetamine.

No description available.

Illicit drug abuse and addiction is a major problem in New Zealand and worldwide with approximately 12% of illicit drug users classified as having drug dependence or drug-use disorders. The chronically relapsing nature of drug addiction is a prominent feature of this disorder and a significant barrier to treating addiction. Amphetamine-type drugs, more than any other class of drugs, have seen an increase in global usage since the early 1990's. The lack of approved medications for the treatment of stimulant addiction together with an increasing treatment demand drives the need for pharmaceutical intervention. Substitute treatment approaches primarily focus on the dopamine (DA) system. However, several lines of research implicate a dual role for serotonin (5-HT). Using a benztropine (BZT) analogue, JHW 007 (JHW), and an atypical antidepressant, trazodone (TRAZ), we sought to test whether the combined modulation of DA and 5-HT during a period of extinction produced greater attenuation to drug-induced reinstatement compared to either DA or 5-HT alone. One hundred and two (102) male Long Evans rats were tested using an extinction-reinstatement model of methamphetamine (MA) addiction in conditioned place preference (CPP) (n=72) and self-administration (n=30) experimental designs. We hypothesised that a combined DA/5-HT treatment would further attenuate MA-induced reinstatement. Findings showed that JHW significantly attenuated MA-induced reinstatement in our self-administration model but not CPP, while TRAZ failed to significantly attenuate reinstatement in both experiments. The combination treatment group showed a mild attenuation to drug seeking with CPP, but this finding was not significant. Due to time restrictions, we did not test the combination group using a self-administration procedure. Unfortunately we were unable to fully address our initially proposed hypothesis, but our results with JHW add further support to this BZT analogue as a promising stimulant abuse medication.

Thesis (Ph.D.)--Tennessee Technological University, 2007. / Bibliography: leaves 82-88.

Thesis (M.A. in Security Studies (Western Hemisphere))--Naval Postgraduate School, June 2008. / Thesis Advisor(s): Giraldo, Jeanne ; Berger, Marcos. "June 2008." Description based on title screen as viewed on August 27, 2008. Includes bibliographical references (p. 67-72). Also available in print.

Thesis (M.A.)--Villanova University, 2008. / Sociology & Criminal Justice Dept. Includes bibliographical references.

Thesis (Ph. D.)--Washington State University, August 2007. / Includes bibliographical references.