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

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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

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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2020-05

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

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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

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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2017-05

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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). While hormone therapies (HT) can treat symptoms of menopause and

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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2014-05

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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 and constantly-changing drug chemical compounds. The project was thoroughly researched

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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2014-05

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Non-Traditional Psychotherapy Techniques: An Assessment of the Value of MDMA, Psilocybin and LSD.

Description

An analysis of the medical the efficacy of MDMA, Psilocybin and LSD as a method of determining the need for psychedelic-based psychotherapy treatments as novel treatments for various psychiatric disorders and how those treatments will be inducted into the United

An analysis of the medical the efficacy of MDMA, Psilocybin and LSD as a method of determining the need for psychedelic-based psychotherapy treatments as novel treatments for various psychiatric disorders and how those treatments will be inducted into the United States in various formats including healthcare, federal law and social acceptance.

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2021-05

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Health & Wealthness Podcast

Description

“Health and Wealthness” is a podcast where your hosts, Emily Weigel and Hanaa Khan, discuss pressing and trending topics about health and wealth that everyone should know about. Our thesis focuses primarily on the opioid epidemic - the science and business sides.

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2021-05

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Health & Wealthness Podcast

Description

Health and Wealthness is a podcast where your hosts, Emily Weigel and Hanaa Khan discuss pressing and trending topics about health and wealth that everyone should know about. Our first four episodes focus on the opioid crisis. Both the science

Health and Wealthness is a podcast where your hosts, Emily Weigel and Hanaa Khan discuss pressing and trending topics about health and wealth that everyone should know about. Our first four episodes focus on the opioid crisis. Both the science and healthcare sides. We then go on to talk about burnout and mental health in a conversational episode.

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2021-05

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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 2 proposed long-term effects of isolated housing (one mouse/cage), when

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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2021-05

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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 the potential to be abused. This was tested using an

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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2013-12

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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 alcohol. Because little research has been conducted on the co-abuse

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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2016-12