Although cannabis is widely consumed by humans for the intoxicating effects that are mediated by delta-9 tetrahydrocannabinol (THC), pre-clinical models of THC self-administration have been difficult to establish. We hypothesized that THC may have reinforcement enhancing effects comparable to other drugs (e.g., nicotine and caffeine), which are also widely consumed by humans but difficult to establish as primary reinforcers in non-human animals. To investigate whether THC is a reinforcement enhancer, male (M, n=8) and female (F, n=8) rats were shaped to self-administer a reinforcing saccharin (SACC) solution (0.2% w/v) in standard operant chambers equipped with infrared beams to monitor locomotor activity. At baseline, we found a significant sex difference for active lever responses and reinforcers earned (F

Progressive-ratio schedules are useful for studying the reinforcing effects of drugs. Earlier human laboratory studies showed that d-amphetamine significantly increased break points relative to placebo. However, the magnitude of the increase was modest, which may be attributable to rather high levels of placebo responding. We used novel response requirements in a modified progressive-ratio procedure and hypothesized that the altered range of response requirements would decrease responding for placebo and increase responding for d-amphetamine. Eight participants completed the study. The participants first sampled oral doses of d-amphetamine (0, 8, 16, and 24mg). In subsequent sessions, the participants were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure with response requirements ranging from 400 to 1800 mouse clicks. A battery of participant-rated drug-effect questionnaires, a performance measure, and cardiovascular measures were included to more fully characterize the effects of d-amphetamine. Placebo maintained low levels of responding. The intermediate dose of d-amphetamine increased responding significantly above placebo levels. d-Amphetamine produced prototypical subject-rated effects that were an orderly function of dose. These data suggest that the modified response requirements resulted in lower levels of placebo taking and a larger separation between the number of placebo and d-amphetamine capsules earned. Behavioural Pharmacology.

Extinguished alcohol-maintained responding has been shown to relapse in aresurgence preparation when food-reinforced responding is subsequently extinguished within the same context. However, drug and nondrug reinforcers are often specific to different contexts. Accordingly, the present experiments sought to determine whether loss of an alternative source of nondrug reinforcement in one context could produce relapse to drug seeking in a separate context. In one experiment, rats made topographically different responses for food or alcohol in alternating components of a multiple schedule. Both reinforcers were delivered during baseline, alcohol was withheld during the second phase of the experiment, and finally both reinforcers were withheld during the final phase. Extinguished alcohol-maintained responding increased upon discontinuation of food deliveries, but may have increased due to similarity between the final experimental phase and an initial training phase. In a second experiment, the training phase that complicated interpretation of the elevated responding observed in Experiment 1 was eliminated altogether. Alcohol seeking again relapsed upon discontinuation of food, suggesting that the training conditions were not the cause of the observed relapse in Experiment 1. Thus, loss of a nondrug reinforcer in one context can produce relapse to drug seeking in another. This procedure may provide a novel model of drug relapse in which loss of context-specific, alternative nondrug reinforcers precipitates relapse to drug seeking in a separate context.

abstract: Greater than 11% of the total population of Americans age 12 and older were illicit drug users with close to 1 million suffering from cocaine use disorder in 2017 alone (SAMHSA, 2017), yet there are no effective pharmacological treatments for this disorder. Previous research from the Neisewander Laboratory in male rats found that administration of a 5-HT1BR agonist facilitates cocaine intake when given prior to a daily self-administration session, while inhibiting cocaine intake and attenuating drug-seeking behavior following 21 days of protracted abstinence, yet it is not known whether such effects are observed in female rats. Women face unique challenges in all phases of the drug addiction cycle. With respect to active drug-taking (i.e., the maintenance phase), women tend to increase their rate of consumption more rapidly than men, and female rats acquire cocaine self-administration faster than males. In part, this is due to ovarian hormone influences on the reinforcing properties of cocaine, where peak levels of endogenous estrogen hormones correspond to an increase in cocaine intake. In this study, we investigated the effects of CP94253, a selective 5HT1BR agonist, on cocaine intake across all phases of the estrous cycle in female rats. The rats were trained to self-administer cocaine (0.75 mg/kg, IV) on a fixed ratio (FR) 5 schedule of reinforcement and daily vaginal smears were taken after each session to monitor the estrous cycle. Rats were pretreated with CP 94,253 (5.6 mg/kg, IP) or vehicle prior to separate tests during each estrous cycle phase and were then either given 1-h access to 0.75 mg/kg cocaine followed by 1-h access to 0.375 mg/kg cocaine or 1-h access to 0.1875 mg/kg cocaine followed by 1-h access to 0.075 mg/kg cocaine. Similar to males, CP 94,253 decreased cocaine intake in females at intermediate doses, however, the estrous cycle phase did not alter this effect. / Dissertation/Thesis / Masters Thesis Biology 2019

FITNESSGRAM is a battery of fitness tests that assess if a child's fitness level is, according to a health standard, enough to be considered healthy. These tests include the five components of health-related fitness: aerobic endurance, muscular strength and muscular endurance, flexibility, and body composition. Students are not compared to each other, but to health fitness standards specific to their age and gender that indicate good health. The purpose of this qualitative study was to identify children's perceptions of FITNESSGRAM and determine if self-administration of this fitness test provides a positive experience for the students. Specifically, this study evaluated (a) students' perceptions of FITNESSGRAM, administered in a self-testing format, (b) children's understanding of the purpose of fitness testing, and (c) what effect participation in FITNESSGRAM had on students' perceptions of their personal health. This study used questionnaires (n = 78), and follow-up individual interviews (n = 45) to identify students' perceptions of FITNESSGRAM. Results using the constant comparative method identified four main categories: (a) administration of fitness testing, (b) the purpose of fitness testing, (c) components of fitness testing, and (d) overall influence of fitness testing. Findings showed that children clearly understood the importance and role of fitness testing, felt successful and were pleased with their results, preferred doing the tests with a partner or by themselves, and thought the fitness test was fun.

Introduction: People with Parkinson's disease require individualised medication regimens to achieve symptomatic control whilst managing complications of the treatments and the underlying disease. Patients should continue to receive their individualised regimen when they are admitted to hospital but studies have highlighted that this may not happen. There is a paucity of research about patients' perceptions of the management of anti-parkinsonian medicines during a hospital admission and the aim of this study was to explore the perceptions of Parkinson's disease patients admitted to Leeds Teaching Hospitals about the management of their anti-parkinsonian medications.Method: Grounded theory methodology was used to allow detailed exploration of patients' perceptions and to generate theory about this under-researched area. Face to face, semi-structured interviews were conducted with 13 Parkinson's disease patients during their hospital admission, fully transcribed and analysed using the constant comparative approach. Results: Categories contributing to the core category of 'patient anxiety' were identified as 'maintaining usual medication routine', 'access to anti-parkinsonian medications', 'accuracy and consistency', 'trust in healthcare professionals' and 'staff knowledge about Parkinson's disease'. Strategies used to manage the anxiety were related to the categories 'utilising expertise' in Parkinson's disease and 'patient involvement' in their care. Discussion: The theory suggests that some patients have negative perceptions about the management of their medicines during a hospital admission. Areas for practice development are presented along with areas for future research. Conclusion: This study provides new insight into the perceptions of patients with Parkinson's disease about the management of their medicines during a hospital admission.

Illicit drug use has been a growing concern over the past few decades. The rise in use of illegal drugs drove the government and law enforcement to aggressively tackle this problem and crackdown on the illicit use of drugs. However, this sparked a further interest in ‘legal highs.’ Before 2011, among the newly popular ‘legal highs’ was ‘Bath Salts.’ Cathinone is a monoamine alkaloid and the active ingredient found in the leaves of the khat plant. The psychoactive form of bath salts may contain a mixture of synthesized cathinones, including, 4-methyl-N-methcathinone (mephedrone), 3,4-methylenedioxy-N- methylcathinone (methylone) and methylenedioxypyrovalerone (MDPV). These three are commonly found in bath salts. One of the major psychoactive ingredients in bath salts is mephedrone. Mephedrone grew in popularity due to its low price, accessibility, and the shortage of MDMA, thus making mephedrone the prime drug to sell as a ‘legal high’ up until 2011 when it became banned in the United S / Pharmaceutical Sciences

Introduction: People with Parkinson's disease require individualised medication regimens to achieve symptomatic control whilst managing complications of the treatments and the underlying disease. Patients should continue to receive their individualised regimen when they are admitted to hospital but studies have highlighted that this may not happen. There is a paucity of research about patients' perceptions of the management of antiparkinsonian medicines during a hospital admission and the aim of this study was to explore the perceptions of Parkinson's disease patients admitted to Leeds Teaching Hospitals about the management of their antiparkinsonian medications.Method: Grounded theory methodology was used to allow detailed exploration of patients' perceptions and to generate theory about this under-researched area. Face to face, semi-structured interviews were conducted with 13 Parkinson's disease patients during their hospital admission, fully transcribed and analysed using the constant comparative approach. Results: Categories contributing to the core category of 'patient anxiety' were identified as 'maintaining usual medication routine', 'access to antiparkinsonian medications', 'accuracy and consistency', 'trust in healthcare professionals' and 'staff knowledge about Parkinson's disease'. Strategies used to manage the anxiety were related to the categories 'utilising expertise' in Parkinson's disease and 'patient involvement' in their care. Discussion: The theory suggests that some patients have negative perceptions about the management of their medicines during a hospital admission. Areas for practice development are presented along with areas for future research. Conclusion: This study provides new insight into the perceptions of patients with Parkinson's disease about the management of their medicines during a hospital admission.

Cocaine dependence is a major health concern worldwide, but despite this high rate of abuse there are currently no approved therapies for cocaine dependence. Replacement pharmacotherapies are one possible approach for treating cocaine dependence, and identification of such therapeutics for cocaine abuse is the long-term goal of this research. Cocaine binds to, and inhibits uptake at the dopamine (DAT), serotonergic (SERT) and noradrenaline (NET) uptake transporters, but studies have shown that cocaine produces its strong behavioural and positive reinforcing effects through inhibition of the DAT. To this end a great number of diverse, non-selective DAT-inhibiting compounds have been investigated as potential cocaine replacement therapies. It was the initial objective of this research to determine whether the behavioral profile of a novel, selective DAT inhibitor, D-84, fit with that thought for an ideal cocaine replacement therapy. Results indicated that D-84 stimulated locomotor activity, incompletely generalized to the cocaine cue in discrimination tests, attenuated cocaine-self-administration and was self-administered. These observations provide a profile consistent, although perhaps not ideal, with one possible treatment strategy for cocaine dependence. Although it is well established that cocaine predominantly produces its abuse-related effects through inhibition of the DAT, recent evidence suggests that inhibition at the SERT may have modulating effects on the pharmacology of cocaine-like compounds. The second part of this dissertation investigated what effects that increasing SERT inhibition had on the cocaine-like behavioural effects of DAT inhibitors, as a method of determining the fruitfulness of incorporating this feature into future drug candidates to improve them. RTI-55 (DAT Ki 2.7 nM SERT Ki 3 nM) and GBR-12909 (DAT Ki 4.3 nM SERT Ki 73 nM) were selected based on their high and intermediate SERT inhibitory effects, respectively. They were compared in behavioural studies with D-84, which is considered to be a selective DAT inhibitor. The results indicated that although increasing SERT inhibition attenuated locomotor activity effects, it had less effect on cocaine-like discriminative stimulus and reinforcing effects, at least with the doses tested

Methamphetamine is a psychomotor stimulant that produces hyperactivity and euphoria and can lead to drug-seeking and abuse. An estimate from 2005 put the cost of methamphetamine abuse to society at an estimated 23.4 billion dollars. One of methamphetamine's effects is activation of glial cells and associated neuroinflammatory activity in the periphery and CNS. Glia are responsible for maintaining calcium homeostasis, neuroplasticity, immune activity, and cell signaling. Activation of glia and neuroinflammation are becoming recognized as links in drug abuse-related behavior. The goal of the present work was to assess the ability of ibudilast, AV1013, and minocycline, three glial cell modulating compounds, to attenuate responding in rodent procedures that model different aspects of methamphetamine abuse-related behavior. First, Ibudilast (1.8, 7.5, 13 mg/kg) and AV1013 (10, 30, 56 mg/kg) were examined for their effects on methamphetamine-induced (3 mg/kg) locomotor activity and sensitization in mice, the latter thought to involve neurocircuitry common with drug relapse. Ibudilast and AV1013 dose-dependently attenuated methamphetamine-induced locomotor activity and its sensitization. Second, ibudilast (1, 7.5, 10 mg/kg), AV1013 (1, 10, 30 mg/kg), and minocycline (10, 30, 60 mg/kg) were examined for their effects on methamphetamine self-administration (0.001, 0.03, and 0.1 mg/kg/inf) in rats. All three compounds significantly reduced methamphetamine (0.03 mg/kg/inf) self-administration. Results suggested baseline self-administration rate as a possible determinant of these effects; however, follow-up tests with ibudilast while controlling for baseline response rate dismissed this possibility. Additional follow-up tests identified whether the attenuation of operant response rates was specific to methamphetamine-maintained behavior. Using a behavioral economic approach, all three test compounds were determined to also affect non-nutritive banana pellet-maintained responding when the baseline strengths maintained by methamphetamine and banana pellet delivery were matched. Finally, ibudilast was evaluated for its effects on methamphetamine discrimination in rats, a procedure thought to model clinical subjective effects. Ibudilast (1, 7.5, 10 mg/kg) did not significantly modify methamphetamine’s discriminative stimulus effects when trained at either 1 or 0.56 mg/kg. These results support the hypothesis that attenuation of glial cell activity and neuroinflammation may be linked to some abuse-related behaviors of methamphetamine, reinforcing their examination as novel targets for treating methamphetamine abuse.