Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2006. / Includes bibliographical references.

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Introduction: In 2021, 2.5 million people aged 12 and older abused the addictive psychostimulant methamphetamine (MA) in the US. MA produces short-lasting euphoria, but also anxiety, erratic behavior, mood disturbance, and abnormal wakefulness. Chronic use of MA can lead to disordered sleep, particularly during withdrawal, and clinical studies have shown that sleep dysfunction is a strong predictor for drug-taking relapse. The neuropeptide hypocretin (HCRT) plays a critical role in the transition to a waking state and also modulates drug reward. Enhanced HCRT signaling in the brain underlies the sleep disorder insomnia and the HCRT-receptor antagonist lemborexant has recently been FDA-approved for treatment of insomnia in humans. Thus, in the current study we characterize sleep dysfunction associated with MA vapor withdrawal and hypothesize that HCRT signaling contributes to negative sleep outcomes. Methods: Adult male Wistar rats (N =8) were implanted with a telemetry device and electroencephalographic/electromyographic signals were recorded for 24 hours (12:12 hours, light:dark cycle). Data were analyzed prior to MA vapor exposure (baseline), and during withdrawal (after one week of MA vapor abstinence). Rats were administered lemborexant (0, and 30 mg/kg, in a counter-balanced order) during withdrawal at the beginning of the light cycle. Results: Rats showed a decrease in time spent in rapid eye movement (REM) sleep in the light cycle during withdrawal, and there was a trend for an increase in time spent in REM sleep during the dark cycle, indicating possible REM sleep rebound. There were no changes to non-REM (NREM) sleep or waking in either the light or dark cycle. The number of bouts of REM sleep decreased during the light cycle, and there was no change in average bout duration in REM sleep during withdrawal compared to baseline. The number of bouts of NREM sleep and waking increased during the dark cycle, while the average bout duration decreased during withdrawal compared to baseline, indicating periods of sleep/wake were more fragmented during the dark cycle. In addition, administration of lemborexant restored the amount of time spent in REM sleep and the number of REM sleep bouts during the light cycle. Conclusions: Overall, these findings show there is a role for HCRT neurotransmission in the observed dysregulated and fragmented sleep of male rats during MA withdrawal. Future research should look at gender differences for sleep dysfunction and MA withdrawal, as well as long-term consequences of MA use.

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Class of 2007 Abstract / Objectives: To identify differences between patients diagnosed with a serious mental illness who test positive for cocaine and/or methamphetamine compared to patients who test positive or other abused substances. Methods: This retrospective study of clinical data obtained through a community mental health agency that provides outpatient services for patients with a serious mental illness. The study population was divided into two subgroups: positive cocaine and/or methamphetamine drug screen versus other positive drug screens and were compared over a 12- month period for the frequency and types of positive drug screens and blood alcohol levels, days of court-ordered treatment, the number of psychiatric hospitalizations and length of stay, primary psychiatric diagnosis, and the cost of care for services provided. Results: More females were in the “cocaine/methamphetamine” group versus more males in the “other substances of abuse” group, (p < 0.01). A higher proportion of patients diagnosed with psychotic disorders tested positive for “other substances” than for “cocaine and methamphetamine” (p < 0.01) and the “cocaine/methamphetamine” group had significantly more mood and anxiety disorders than the other group (p < 0.05). The frequency of patients testing positive for marijuana, methadone, and other opiates was higher in the “other substance abuse” group (p < 0.001). Patients in the “cocaine/methamphetamine” group had higher rates of polysubstance abuse (p < 0.001). The most commonly abused substance was cocaine (53.8%). Conclusions: Regular drug screening for substances of abuse and utilization of drug treatment programs should be recommended for SMI patients to improve their care and treatment outcomes.

Despite the fact that the database documenting amphetamine-related effects in humans has increased over the past decade, there remain important gaps in our knowledge of the effects of these drugs in humans. The current investigations, which examined the acute, repeated-dose and residual effects of amphetamine derivatives on various psychological measures in humans, addressed two of these gaps. The first was the lack of empirical evidence directly comparing d-amphetamine and methamphetamine. Study 1 was the first direct comparison of the regulatory focus effects of intranasal d-amphetamine and methamphetamine (12, 50 mg/70kg). Results indicate that the drugs produced overlapping effects on most measures (e.g. increased "prevention" focus state and task engagement). Under the low dose condition, only methamphetamine increased "prevention" focus. Study 2 was a within-participant investigation on the impact of three 3,4-methylenedioxymethamphetamine (MDMA) administrations (12 and 24 hours intervals) on physiological, subjective, and behavioral measures in experienced MDMA users. Heart rate, blood pressure, oral temperature, subjective effects, psychomotor performance, and sleep were assessed repeatedly throughout the study. Acute administration of MDMA produced systematic increases in heart rate, blood pressure, and subjective effects, but oral temperature was unaltered. Following repeated drug administration, heart rate elevations were no longer statistically significant; blood pressure and subjective-effect ratings remained significantly increased, but such increases were diminished relative to acute drug effects. Measures of sleep were decreased only on the evening following two active MDMA administrations. Performance alterations were not observed nor were MDMA-related toxic effects. Overall, the data from both studies do not support either: 1) the conventional notion that d-amphetamine and methamphetamine produce markedly different effects in humans; or 2) the general perception that MDMA produces dangerous cardiovascular and subjective effects in humans following repeated administration.

abstract: Serotonin 1B receptors (5-HT1BRs) are a novel target for developing pharmacological therapies to reduce psychostimulant craving. 5-HT1BRs are expressed in the mesolimbic pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), which is involved in reward and motivation. 5-HT1BR agonists modulate both cocaine- and methamphetamine-seeking behaviors in rat models of psychostimulant craving. In this dissertation, I tested the central hypothesis that 5-HT1BRs regulate cocaine and methamphetamine stimulant and rewarding effects in mice. I injected mice daily with cocaine for 20 days and then tested them 20 days after their last injection. The results showed that the 5-HT1BR agonist CP94253 attenuated sensitization of cocaine-induced locomotion and cocaine-seeking behavior, measured as a decrease in the ability of a cocaine priming injection to reinstate extinguished cocaine-conditioned place preference (CPP). Subsequent experiments showed that CP94253 given prior to conditioning sessions had no effect on acquisition of methamphetamine-CPP, a measure of drug reward; however, CP94253 given prior to testing attenuated expression of methamphetamine-CPP, a measure of drug seeking. To examine brain regions and cell types involved in CP94253 attenuation of methamphetamine-seeking, I examined changes in the immediate early gene product, Fos, which is a marker of brain activity involving gene transcription changes. Mice expressing methamphetamine-CPP showed elevated Fos expression in the VTA and basolateral amygdala (BlA), and reduced Fos in the central nucleus of the amygdala (CeA). In mice showing CP94253-induced attenuation of methamphetamine-CPP expression, Fos was increased in the VTA, NAc shell and core, and the dorsal medial caudate-putamen. CP94253 also reversed the methamphetamine-conditioned decrease in Fos expression in the CeA and the increase in the BlA. In drug-naïve, non-conditioned control mice, CP94253 only increased Fos in the CeA, suggesting that the increases observed in methamphetamine-conditioned mice were due to conditioning rather than an unconditioned effect of CP94253 on Fos expression. In conclusion, 5-HT1BR stimulation attenuates both cocaine and methamphetamine seeking in mice, and that the latter effect may involve normalizing activity in the amygdala and increasing activity in the mesolimbic pathway. These findings further support the potential efficacy of 5-HT1BR agonists as pharmacological interventions for psychostimulant craving in humans. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2018

Magister Artium (Psychology) - MA(Psych) / Substance use among pregnant women is a perennial problem in the Western Cape Province of South Africa. There are many influential factors are associated with substance use among women of childbearing-age. The study explored factors associated with substance use among pregnant women using a qualitative research design and the bio-ecological theoretical framework to explore and guide the researcher throughout the study. Participants were selected using purposive sampling. Only participants accessed from the Department of Social Development meeting the inclusion criteria of the study were interviewed using semi-structured interviews. Immediate referral for psychological intervention during the interview was available for participants who needed it. Braun and Clarke’s (2006) six phases of thematic analysis were utilised to analyse the data. The study adheres to ethical guidelines for the participants’ protection. Participants were informed about the study before the initiation of the interviews and the details of their voluntary participation were explained. The key findings from this study illustrate that socio-cultural factors, personal factors, emotional response and intimate relationships are the major contributing factors to substance use among pregnant women in this sample. The results outline the preventative measures that pregnant women implement. Lastly, the study reveals the positive and negative perceptions of substance use programmes that participants share. Some of the study findings are similar to the existing literature and some of the findings differed. Recommendations emanating from the study include that the stakeholders, rehabilitation centres, Department of Health and future researchers should act proactively against substance use during pregnancy.

Violent crime and aggressive behaviour are of increasing concern in New Zealand. Much of this is displayed by adolescent males who have an association with some form of substance use, abuse or dependence. This is especially relevant for stimulant drugs, especially methamphetamine (MA), and 1-benzylpiperazine (BZP). Previous research has shown that BZP has similar neurochemical and behavioural effects to MA, and there is a large volume of research showing an association between chronic MA use and aggression. In contrast to this, there has been little research into the consequences of a single administration of MA, which is often portrayed by the media as having the same detrimental effects as chronic use. The present study was designed to determine whether or not acute MA would induce aggressive behaviour in adolescent male hooded rats. In addition, the study also examined whether BZP had a similar effect to MA. Sixty male hooded rats aged between 41 to 50 postnatal days (PND), were utilised and divided into five groups of 12 rats each: saline; 1mg/kg (low dose) or 2mg/kg (high dose) MA; 10mg/kg (low dose) or 20mg/kg (high dose) BZP. The rats were tested using the resident/intruder test of aggression, consisting of eight measures of aggressive behaviour. The results suggested that, rats treated with either a low or high dose of MA or BZP were significantly less aggressive than saline-treated rats. There appeared to be little to distinguish between the two drugs in their effects on the responses recorded. It was concluded that an acute administration of either MA or BZP did not increase aggression, and thus did not support the view that aggression will result from a single dose of MA (or indeed BZP that has not been previously investigated in this context).

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains xvi, 177 p. : ill. (some col.), col. map. Vita. Includes abstract. Includes bibliographical references (p. 167-171).