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How might abandoning rodent models help advance schizophrenia research?

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Animal models have led to important discoveries in biomedical research; their utility to psychiatry and comparative neuroscience is less clear. Disorders of higher-order brain function, schizophrenia chief among them, have proven exceptionally elusive to model. Schizophrenia researchers are of two

Animal models have led to important discoveries in biomedical research; their utility to psychiatry and comparative neuroscience is less clear. Disorders of higher-order brain function, schizophrenia chief among them, have proven exceptionally elusive to model. Schizophrenia researchers are of two minds about the possibility of modeling the schizophrenia phenotype(s) in laboratory animals: at one and the same time they are both pessimistic and pragmatic. That is, they admit the discouraging difficulty of the task, and yet proceed, apparently undeterred, with putative animal models of schizophrenia, as if the criticisms that yield the pessimistic judgments simply do not matter. In this article, we survey the criticisms and evaluate their merits. We then ask: what would it mean to take seriously the claim that modeling schizophrenia in at least some non-human animals - namely, rodents - is doomed, futile, impossible? How would, and how should, schizophrenia research be undertaken were the current animal models rejected as simply inadequate to the task? Our aim is not to disparage sound research into the etiology, symptomatology, and treatment of schizophrenia, but rather to emphasize the scope of the gap between current and optimal research practices. We conclude with recommendations to reinvigorate the quest to understand, prevent, and treat schizophrenia.

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2018-12

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An Evaluation of the Levonorgestrel-Releasing Intrauterine Device and its Impact on Cognitive Function in a Rat Model

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The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx)

The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a Blank IUD (without Levo), or a Levo-releasing IUD (Levo IUD), enabling us to evaluate the effects of Ovx and the effects of IUD administration on cognition. Two weeks after surgery, all treatment groups were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. At sacrifice, upon investigation of the uteri, it was determined that some of the IUDs were no longer present in animals from these groups: Sham\u2014Blank IUD, Ovx\u2014Blank IUD, and Sham\u2014Levo IUD. Results from the remaining three groups showed that compared to Sham animals with no IUDs, Ovx animals with no IUDs had marginally impaired working memory performance, and that Ovx animals with Levo IUDs as compared to Ovx animals with no IUDs had marginally enhanced memory performance, not specific to a particular memory type. Results also showed that Ovx animals with Levo IUDs had qualitatively more cells in their vaginal smears and increased uterine horn weight compared to Ovx animals with no IUDs, suggesting local stimulation of the Levo IUDs to the uterine horns. Overall, these results provide alternative evidence to the hypothesis that the Levo IUD administers Levo in solely a localized manner, and suggests that the possibility for the Levo IUD to affect reproductive cyclicity in ovary-intact animals is not rejected. The potential for the Levo IUD to exert effects on cognition suggests that either the hormone does in fact systemically circulate, or that the Levo IUD administration affects cognition by altering an as yet undetermined hormonal or other feedback between the uterus and the brain.

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2018-12

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Thinking Brains: An Introduction to Neuroscientific Thought

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An introduction to neuroscientific thought aimed at an audience that is not educated in biology. Meant to be readable and easily understood by anyone with a high school education. The first section is completed in its entirety, with outlines for

An introduction to neuroscientific thought aimed at an audience that is not educated in biology. Meant to be readable and easily understood by anyone with a high school education. The first section is completed in its entirety, with outlines for the proposed final sections to be completed over the next few years.

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2014-05

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Measuring the Double-Edged Sword: Does Scientifically Deterministic Evidence Protect or Punish Criminals?

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Scientists, lawyers, and bioethicists have pondered the impact of scientifically deterministic evidence on a judge or jury when deciding the sentence of a criminal. Though the impact may be one that relieves the amount of personal guilt on the part

Scientists, lawyers, and bioethicists have pondered the impact of scientifically deterministic evidence on a judge or jury when deciding the sentence of a criminal. Though the impact may be one that relieves the amount of personal guilt on the part of the criminal, this evidence may also be the very reason that a judge or jury punishes more strongly, suggesting that this type of evidence may be a double-edged sword. 118 participants were shown three films of fictional sentencing hearings. All three films introduced scientifically deterministic evidence, and participants were asked to recommend a prison sentence. Each hearing portrayed a different criminal with different neurological conditions, a different crime, and a different extent of argumentation during closing arguments about the scientifically deterministic evidence. Though the argumentation from the prosecution and the defense did not affect sentencing, the interaction of type of crime and neurological condition did.

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2014-05

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An analysis of how narcocorridos portray the political sociology of the Mexican Drug cartels in Mexican society

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Since the collapse of the Medellin Cartel in Colombia in 1993, the Mexican drug cartels have been increasing in strength and international presence. Along with the organization's political and economic involvement, a deeply rooted culture has been developing. Three distinct

Since the collapse of the Medellin Cartel in Colombia in 1993, the Mexican drug cartels have been increasing in strength and international presence. Along with the organization's political and economic involvement, a deeply rooted culture has been developing. Three distinct time periods define this culture: pre-Medellin Cartel collapse (1970s-1993), post-Medellin Cartel Collapse (1993-2006) and post-President Calderon's Drug War announcement (2006-present day). More specifically, the history and fascination with the cartel is documented in songs, known as narcocorridos, which celebrate and support the drug cartels. The science of political sociology addresses the power relationship that exists between a state, its citizens, and the state's social groups. This study investigates the political sociology of each period, specifically how society viewed the cartel and their roles within the cartel. I argue that the narcocorridos accurately describe the evolution of narcoculture in Mexican society. This study consists of analyses of narcocorrido song lyrics, the political sociology of each time period, and finally, the societal perception of the drug cartel. First, I will evaluate the most popular songs' lyrics of the three defining time periods in the Mexican Drug Cartel history. Next, I will analyze the lyrics and determine whether or not they accurately reflect the political sociological features of the time period. Last, I will discuss what the societal perceptions of being associated with the cartel were during each time period. This study concludes by hypothesizing what the future of narcocorriodos will be. This prediction will demonstrate how the songs will continue to reflect the political sociology of the time period, including the societal attitudes towards the cartel.

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2016-05

Joint Action Produces Super Mirror Neurons

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Abstract: Behavioral evidence suggests that joint coordinated movement attunes one's own motor system to the actions of another. This attunement is called a joint body schema (JBS). According to the JBS hypothesis, the attunement arises from heightened mirror neuron sensitivity

Abstract: Behavioral evidence suggests that joint coordinated movement attunes one's own motor system to the actions of another. This attunement is called a joint body schema (JBS). According to the JBS hypothesis, the attunement arises from heightened mirror neuron sensitivity to the actions of the other person. This study uses EEG mu suppression, an index of mirror neuron system activity, to provide neurophysiological evidence for the JBS hypothesis. After a joint action task in which the experimenter used her left hand, the participant's EEG revealed greater mu suppression (compared to before the task) in her right cerebral hemisphere when watching a left hand movement. This enhanced mu suppression was found regardless of whether the participant was moving or watching the experimenter move. These results are suggestive of super mirror neurons, that is, mirror neurons which are strengthened in sensitivity to another after a joint action task and do not distinguish between whether the individual or the individual's partner is moving.

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2015-12

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Functional Switch in the Role of 5-HT1B Receptors as a Result of Cocaine Withdrawal in Mice

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Substance abuse disorders affect 15.3 million people worldwide. The field has primarily focused on dopaminergic drugs as treatments for substance use disorders. However, recent work has demonstrated the potential of serotonergic compounds to treat substance abuse. Specifically, the serotonin 1B

Substance abuse disorders affect 15.3 million people worldwide. The field has primarily focused on dopaminergic drugs as treatments for substance use disorders. However, recent work has demonstrated the potential of serotonergic compounds to treat substance abuse. Specifically, the serotonin 1B receptor (5-HT1BR), a Gi-coupled receptor located throughout the mesocorticolimbic dopamine system, has been implicated in the incentive motivational and rewarding effects of cocaine. Our research suggests that the stimulation of 5-HT1BRs produces different effects at various time points in the addiction cycle. During maintenance of chronic cocaine administration, 5-HT1BR stimulation has a facilitative effect on the reinforcing properties of cocaine. However 5-HT1BR stimulation exhibits inhibitory effects on reinforcement during prolonged abstinence from cocaine. The aim of this study was to examine the possibility of a switch in the functional role of 5-HT1BRs in the locomotor effects of cocaine at different time points of chronic cocaine administration in mice. We found that the 5-HT1BR agonist CP 94,253 increased locomotor activity in mice tested one day after the last chronic cocaine administration session regardless of whether the chronic treatment was cocaine or saline and regardless of challenge injection (i.e., cocaine or saline). Yet after abstinence, CP 94,253 induced a decrease in locomotor activity in mice challenged with saline and attenuated cocaine-induced locomotion relative to cocaine challenge after vehicle pretreatment. These findings suggest that a switch in the functional role of 5-HT1BR is observed at different stages of the addiction cycle and further suggest that clinical applications of drugs acting on 5-HT1BR should consider these effects.

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2014-05

The Relation between Anxiety and Conditioned Place Preference to Methamphetamine in Female versus Male Rats

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Females are highly vulnerable to the effects of methamphetamine, and understanding the mechanisms of this is critical to addressing methamphetamine use as a public health issue. Hormones may play a role in methamphetamine sensitivity; thus, the fluctuation of various endogenous

Females are highly vulnerable to the effects of methamphetamine, and understanding the mechanisms of this is critical to addressing methamphetamine use as a public health issue. Hormones may play a role in methamphetamine sensitivity; thus, the fluctuation of various endogenous peptides during the postpartum experience is of interest. This honors thesis project explored the relation between anxiety-like behavior, as measured by activity in an open field, and conditioned place preference to methamphetamine in female versus male rats. The behavior of postpartum as well as virgin female rats was compared to that of male rats. There was not a significant difference between males and females in conditioned place preference to methamphetamine, yet females showed higher locomotor activity in response to the drug as well as increased anxiety-like behavior in open field testing as compared to males. Further study is vital to comprehending the complex mechanisms of sex differences in methamphetamine addiction.

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2016-05

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Cognitive Impact of Dietary Phytoestrogens

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There is preclinical evidence that the detrimental cognitive effects of hormone loss can be ameliorated by estrogen therapy (Bimonte, Acosta, & Talboom, 2010), however, one of the primary concerns with current hormone therapies is that they are nonselective, leading to

There is preclinical evidence that the detrimental cognitive effects of hormone loss can be ameliorated by estrogen therapy (Bimonte, Acosta, & Talboom, 2010), however, one of the primary concerns with current hormone therapies is that they are nonselective, leading to increased risk of breast and endometrial cancers as well as heart disease. Thus, in order to achieve a successful and clinically relevant long-term hormone therapy option, it is optimal to find an estrogen therapy regimen that is selective to its target tissue. Recently, phytoestrogens have been found to exert selective, beneficial effects on cognition and brain. For example, genistein and diadzein produce neuroprotective effects in cognitive brain regions (Zhao, Chen, & Diaz Brinton, 2002). The purpose of this study was threefold: 1) to examine the cognitive impact of phytoestrogens in young ovariectomized rats, 2) to replicate the dose effects found in the Luine study (Luine et al., 2006), while controlling for manufacturer differences, and 3) to assess if the rodent diet used in our laboratory has an estrogenic-like cognitive impact.The current findings suggest that, at least for object memory, diets containing varying amounts of phytoestrogens can alter cognition, with diets containing high amounts of phytoestrogens showing potential benefits to this type of memory.

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2013-05

A Methodology for Determining the Dendritic Complexity of Hippocampal Neurons in Chronically Stressed Rats

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Chronic stress is a risk factor for many diseases that impact the brain, including Alzheimer’s Disease. Unlike acute stress, chronic stress reduces neuronal plasticity, which can lead to neuronal remodeling and suppression. This project investigates the effect of stress on

Chronic stress is a risk factor for many diseases that impact the brain, including Alzheimer’s Disease. Unlike acute stress, chronic stress reduces neuronal plasticity, which can lead to neuronal remodeling and suppression. This project investigates the effect of stress on the dendritic complexity of hippocampal neurons in rats, demonstrating a methodology for procuring and analyzing these neurons. The brains of the 160 rats from the Sustained Threat and Timing (STAT) experiment were frozen. The STAT experiment investigated the effect chronic variable stress had on prospective and retrospective timing in rodents. Using a cryostat, thin coronal slices of brain tissue were placed on microscopic slides. The tissue samples were then stained using the Golgi method of silver staining. Hippocampal neurons were assessed using Sholl Analysis; the dendritic complexity of these neurons was quantified. The method of using Sholl Analysis was found to be an effective process in measuring dendritic length of hippocampal neurons.

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2020-05