Matching Items (14)

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The Chase for a Legal High: Discovering What Arizonans Know About Designer Drugs

Description

This creative project explores the trend of designer/synthetic drug use in Arizona and nationwide. The project serves as "gap research" - bringing to light the problem of limited use statistics

This creative project explores the trend of designer/synthetic drug use in Arizona and nationwide. The project serves as "gap research" - bringing to light the problem of limited use statistics and constantly-changing drug chemical compounds. The project was thoroughly researched using media reports, psychology/drug addiction experts, community education organizers and available healthcare statistics. The results provided not definitive answer other than that more work needs to be done in the area of synthetic drug use. Parents and youth must educate themselves on the dangers of using these "legal" drugs.

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Created

Date Created
  • 2014-05

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Understanding the Impact of Phytoestrogens on Memory & the Cholinergic System

Description

Menopause is reproductive senescence characterized by a loss of ovarian estrogen and progesterone. Women can experience cognitive decline and other negative symptoms with the loss of ovarian hormones (Sherwin, 2006).

Menopause is reproductive senescence characterized by a loss of ovarian estrogen and progesterone. Women can experience cognitive decline and other negative symptoms with the loss of ovarian hormones (Sherwin, 2006). While hormone therapies (HT) can treat symptoms of menopause and may have neuroprotective properties, such as the potential to decrease the risk of Alzheimer's Disease (Behl & Manthey, 2000), there are many effects of current HTs that are not ideal. Indeed, optimizing conventional HTs has proven complex, indicating a need for alternative therapies. Phytoestrogens are estrogenic compounds found naturally in plants such as soybeans, that could provide new treatment options. Dietary phytoestrogens can benefit memory in the rodent model (Luine, 2006), although the mechanism underlying these effects is unclear. Basal forebrain cholinergic projections have been shown to mediate the cognitive benefits of estrogen (Gibbs, 2010); we hypothesize that phytoestrogens act similarly, via the cholinergic system, to impact memory. We administered varying doses of phytoestrogen-containing diets to ovariectomized female rats, and used the place recognition task to evaluate spatial memory. Brains were then analyzed for choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, in the vertical-diagonal bands (VDB) and the medial septum (MS) of the basal forebrain. Results showed that ChAT cell counts in the VDB were marginally higher with dietary phytoestrogen treatment. Further, VDB ChAT cell counts positively correlated with place recognition performance, indicating that animals with more VDB ChAT neurons exhibited better spatial memory performance. These results suggest that phytoestrogens might act similarly to natural, endogenously circulating estrogens, and identify phytoestrogens as a direction for investigation as a HT.

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Created

Date Created
  • 2014-05

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Intracranial Self-Stimulation and the Abuse Potential of the Synthetic Cathinones: Methylone and α-PVP

Description

In recent years the abuse of synthetic cathinones, "Bath Salts," has increased. The purpose of this study was to analyze two synthetic cathinones, methylone and α-pvp, for hedonic properties or

In recent years the abuse of synthetic cathinones, "Bath Salts," has increased. The purpose of this study was to analyze two synthetic cathinones, methylone and α-pvp, for hedonic properties or the potential to be abused. This was tested using an intracranial self-stimulation paradigm, a robust measurement for reward. It was found methylone resulted in an abuse potential similar to MDMA, ecstasy, abuse. Moreover, the results for α-pvp showed a high liability for abuse.

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Created

Date Created
  • 2013-12

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D3 receptor related drugs MC-250041 and LS-3-134 and their effects on locomotor activity and motivation for cocaine

Description

Abstract Cocaine is highly addictive because it exacerbates the action responsible for creating the feeling of "reward," which is controlled by the neurotransmitter dopamine. Dopamine receptors can be divided into

Abstract Cocaine is highly addictive because it exacerbates the action responsible for creating the feeling of "reward," which is controlled by the neurotransmitter dopamine. Dopamine receptors can be divided into five subtypes: D1, D2, D3, D4, and D5. The localization of D3 receptors is restricted to the mesolimbic pathway, which is often called the "reward pathway." This pathway is associated with emotions, motivation, and behavior. There is evidence that these receptors are upregulated in response to the repeated use of psychostimulants, such as cocaine, making these receptors a potential target for pharmaceutical therapeutics for drug addiction. In the present study, two compounds selective for D3 receptors, MC-250041 and LS-3-134, were examined for their effects on spontaneous and cocaine-primed locomotor activity. The present study also aimed to examine the effects of MC-250041 and LS-3-134 on the number of lever presses and infusions under a progressive ratio (PR) schedule when subjects are trained to self-administer cocaine within an operant conditioning chamber. Based on the present research on D3 receptor compounds and D3Rs, I hypothesized that pretreatment with MC-250041 or LS-3-134 decreases cocaine self-administration under a progressive ratio (PR) schedule of cocaine reinforcement at doses that would have no effect on locomotor activity. The results showed no significant effects on spontaneous or cocaine-primed locomotor activity following an injection of MC-250041 (1, 3, 5.6 mg/kg IP). Similarly, there was no change in the amount of lever presses or drug infusions within an operant conditioning chamber at any of the examined doses of MC-250041 (3, 5.6, 10 mg/kg IP) during self-administration. LS-3-134 decreased cocaine-primed locomotor activity, as well as lever presses and infusions during self-administration at the 5.6 mg/kg dose; however, there was no effect on spontaneous locomotor activity at any of the examined doses (1, 3.2, 5.6 mg/kg IP). In conclusion, the results of the study suggest that LS-3-134 effectively reduced motivation for cocaine at the 5.6 mg/kg dose; whereas, MC-250041 was unsuccessful at warranting any significant effect on motivation for cocaine at any of the examined doses.

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Created

Date Created
  • 2017-05

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Motor Learning Loss Due to MEK1 Hyperactivation in Cortical Excitatory Neurons

Description

Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects

Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My research focuses on defining the relationship between increased ERK/MAPK signaling and its effects on the nervous system, specifically in the context of motor learning. Motor function depends on several neuroanatomically distinct regions, especially the spinal cord, cerebellum, striatum, and cerebral cortex. We tested whether hyperactivation of ERK/MAPK specifically in the cortex was sufficient to drive changes in motor function. We used a series of genetically modified mouse models and cre-lox technology to hyperactivate ERK/MAPK in the cerebral cortex. Nex:Cre/NeuroD6:Cre was employed to express a constitutively active MEK mutation throughout all layers of the cerebral cortex from an early stage of development. RBP4:Cre, caMEK only exhibited hyper activation in cortical glutamatergic neurons responsible for cortical output (neurons in layer V of the cerebral cortex). First, the two mouse strains were tested in an open field paradigm to assess global locomotor abilities and overall fitness for fine motor tasks. Next, a skilled motor reaching task was used to evaluate motor learning capabilities. The results show that Nex:Cre/NeuroD6:Cre, caMEK mutants do not learn the motor reaching task, although they performed normally on the open field task. Preliminary results suggest RBP4:Cre, caMEK mutants exhibit normal locomotor capabilities and a partial lack of learning. The difference in motor learning capabilities might be explained by the extent of altered connectivity in different regions of the corticospinal tract. Once we have identified the neuropathological effects of various layers in the cortex we will be able to determine whether therapeutic interventions are sufficient to reverse these learning defects.

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Date Created
  • 2016-12

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The Combined Effects of Methamphetamine and Alcohol on Brain Reward Function as Assessed Using Intracranial Self-Stimulation

Description

Polysubstance abuse is far more common than single substance abuse. One of the most widely abused, yet greatly understudied combination of drugs is the simultaneous use of methamphetamine (meth) and

Polysubstance abuse is far more common than single substance abuse. One of the most widely abused, yet greatly understudied combination of drugs is the simultaneous use of methamphetamine (meth) and alcohol. Because little research has been conducted on the co-abuse of meth and alcohol, it is important to study the behavioral and neural mechanisms underlying the use of both to combat addiction and come closer to finding an effective treatment of this form of drug abuse. This study uses a rodent model to attempt to identify the mechanisms underlying this co-abuse through the stimulation of the medial forebrain bundle (MFB) and thus the activation of the mesocorticolimbic pathway, the brain's pleasure circuit. First, self-stimulation thresholds (the lowest electrical current the rats are willing to respond for) were determined using a process called Discrete Trials Training. This threshold was later used as a baseline measure to reference when the rats were administered the drugs of abuse: meth and alcohol, both alone and in combination. Our overall results did not show any significant effects of combining alcohol and meth relative to the effects of either drug alone, although subject attrition may have resulted in sample sizes that were statistically underpowered. The results of this and future studies will help provide a clearer understanding of the neural mechanisms underlying the polyabuse of meth and alcohol and can potentially lead to more successfully combating and treating this addiction.

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Date Created
  • 2016-12

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Peace, Love, Unity, Respect, and Responsibility: Attitudes on Psychedelic Harm Reduction in the EDM Community

Description

In this field study, 103 individuals from two different music festivals, one in California and one in Michigan, were surveyed to observe current attitudes surrounding harm reduction strategies associated with

In this field study, 103 individuals from two different music festivals, one in California and one in Michigan, were surveyed to observe current attitudes surrounding harm reduction strategies associated with psychedelic drug usage in the EDM scene. Topics from the survey included but were not limited to the chemical testing of substances, frequency of usage, spacing between usage, and adverse effects associated with usage. It was concluded that harm reduction education should become more integrated within the EDM scene in order to provide research-based evidence for ravers to make better decisions for their health. While authorities have pushed "just say no", the lack of education altogether in the community is life threatening. Education is the key to saving minds, bodies, and lives.

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Date Created
  • 2016-12

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5-HT1B receptor agonist CP 94,253 reduces cocaine intake in female rats post-abstinence and after resuming self-administration

Description

Approximately five million Americans suffer from cocaine use disorder with no FDA approved pharmaceutical to help their path to recovery (Yerby, 2019). Serotonin is heavily implicated in cocaine use and

Approximately five million Americans suffer from cocaine use disorder with no FDA approved pharmaceutical to help their path to recovery (Yerby, 2019). Serotonin is heavily implicated in cocaine use and in the reward system, and is therefore a suggested target for pharmaceuticals aiming to aid in psychostimulant addiction (Sarlin, 2019; Clark and Neumaier, 2001). CP 94,253, a 5-HT1BR agonist, has been shown to increase cocaine intake during maintenance of daily cocaine self-administration, though it has also been shown to decrease intake after a period of forced abstinence (Parsons et al., 1998; Pentowski et al., 2009). While a decrease in cocaine intake post-abstinence is promising post-abstinence, it remains to be seen whether this is a viable option if patients relapse. Most experiments are conducted with male rats, though an increasing amount of data has come to light on the differing effects of drugs on male and female rats (Mennenga and Bimonte-Nelson, 2014). Previous studies conducted through our lab have shown no difference in cocaine self-administration behavior across the estrous cycle phases with CP 94,253. It remains to be seen however, whether CP 94,253 would function dissimilarly in female rats than in male rats. This experiment studied the effects of CP 94,253 on post-abstinence and post-resumption cocaine self-administration in free-cycling female rats across two doses of cocaine. It was shown that CP 94,253 reduces cocaine intake both post-abstinence and post-resumption, suggesting that this pharmacotherapy would work in cases of relapse, and that there are no sex differences in its effects. While more studies should be conducted with locomotion and stress tests, thus far this experiment provides further evidence for the validity of CP 94,253 to be a promising pharmacotherapeutic option for future investigation.

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Created

Date Created
  • 2020-05

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Effects of Adolescent Social Isolation on Behavioral Inhibition and Ethanol Preference in Mice

Description

Exploration of a mouse model (C57BL/6J) capable of demonstrating behavioral changes after adolescent social isolation that are consistent with prior findings may prove beneficial in later research. This study examined

Exploration of a mouse model (C57BL/6J) capable of demonstrating behavioral changes after adolescent social isolation that are consistent with prior findings may prove beneficial in later research. This study examined 2 proposed long-term effects of isolated housing (one mouse/cage), when compared to group housing (two mice/cage) during adolescence. Mice were placed in their respective housing conditions after weaning (PND 21) and remained in those conditions until PND 60. The same cohorts were used in both phases of the experiment. Phase 1 sought to confirm previous findings that showed increases in ethanol intake after adolescent social isolation using a 2-bottle preference Drinking-in-the-Dark (DID) design over a 4-day period (PND 64-PND 67.). Phase 2 sought to elucidate the effects present after adolescent social isolation, as measured using response inhibition capabilities demonstrated during fixed-minimum interval (FMI) trials (PND 81-PND 111). Findings in phase 1 of the experiment were non-significant, save a strong tendency for female mice in both housing conditions to drink more as a proportion of their bodyweight (g/kg). However, a trend of lower bodyweight in single housed mice did exist, which does suggest that detrimental stress was applied via the used of adolescent isolation in that housing condition. Findings in phase 2 showed little effect of adolescent social isolation on mean inter-response time (IRT) at any criterion used (FMI-0, FMI-4, FMI-6). Evaluation of mean interquartile range (IQR) of IRTs showed a significantly greater amount of variation in IRT responses within single housed mice at the highest criterion (FMI-6), and a trend in the same direction when FMI-4 and FMI-6 were tested concurrently. Taken as a whole, the findings of this experiment suggest that the effect of adolescent social isolation on ethanol intake is far less robust than the effect of sex and may be difficult to replicate in a low-power study. Additionally, adolescent social isolation may interfere with the ability of mice to show consistent accuracy during FMI tasks or a delay in recognition of FMI criterion change.

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Date Created
  • 2021-05

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A Mouse Model of Serotonin 1B Receptor Modulation of Cocaine and Methamphetamine Craving

Description

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)

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.

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Agent

Created

Date Created
  • 2018