Matching Items (5)
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- All Subjects: Neuroscience
- Creators: Neisewander, Janet
Description
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.
ContributorsBrunwasser, Samuel Joshua (Author) / Neisewander, Janet (Thesis director) / Pentkowski, Nathan (Committee member) / Der-Ghazarian, Taleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2014-05
Description
Cocaine is a highly addictive psychostimulant that is widely used around the world. It is far more cost effective to curb this problem through treatment than by any other method as medicinal drug treatment is 15 times more effective than law enforcement at reducing the societal costs of cocaine use as determine by RAND corp. In a previous paper from our lab, it was found that via virally mediated introduction of additional 5-HT1B receptors into the nucleus accumbens there was a leftward shift in the cocaine intake dose-response curve in animals that were self-administering cocaine by pressing a lever. These findings suggest that 5-HT1B receptor action enhances the reinforcing effects of cocaine. However, when animals were given a 21-day period of prolonged abstinence and then tested for cocaine intake, it was determined that 5-HT1B receptor action had the opposite effect of decreasing cocaine intake presumably due to a decrease in the reinforcing effects of cocaine: [16]. The experiment in the current paper was devised to further test this finding via pharmacological means using the 5-HT1B agonist CP 94253 to increase stimulation of 5-HT1B receptors. Animals were trained to self-administer by pressing a lever on fixed ratio schedules of cocaine reinforcement given at 0.75 mg/kg and 0.075 mg/kg doses of cocaine. These doses allowed us to examine changes in self-administration on both the ascending and descending limbs of the inverted u-shaped cocaine dose-effect curve. Our results indicated that in animals given CP 94253 exhibited a decrease in responding on both the ascending and descending limbs of the dose response curve demonstrating a downward shift after prolonged abstinence. These exciting results suggest that the agonist decreases cocaine intake, and therefore, the agonist may be a useful treatment for cocaine dependence.
ContributorsYanamandra, Krishna Teja (Author) / Neisewander, Janet (Thesis director) / Goldstein, Elliott (Committee member) / Pentkowski, Nathan (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
As the incidence of dementia continues to rise, the need for an effective and non-invasive method of intervention has become increasingly imperative. Music therapy has exhibited these qualities in addition to relatively low implementation costs, therefore establishing itself as a promising means of therapeutic intervention. In this review, current research was investigated in order to determine its effectiveness and uncover the neurochemical mechanisms that lead to positive manifestations such as improved memory recall, increased social affiliation, increased motivation, and decreased anxiety. Music therapy has been found to improve several aspects of memory recall. One proposed mechanism involves temporal entrainment, during which the melodic structures present in music provide a framework for chunking information. Although entrainment's role in the treatment of motor defects has been thoroughly studied, its role in treating cognitive disorders is still relatively new. Musicians have also been shown to demonstrate extensive plastic changes; therefore, it is hypothesized that non-musicians may also glean some benefits from engaging in music. Social affiliation has been found to increase due to increases in endogenous oxytocin. Oxytocin has also been shown to strengthen hippocampal spike transmission, a promising outcome for Alzheimer's patients. An increase in motivation has also been found to occur due to music's ability to tap into the reward center of the brain. Dopaminergic transmission between the VTA, NAc and higher functioning regions such as the OFC and hypothalamus has been revealed. Additionally, relaxing music decreases stress levels and modifies associated autonomic processes, i.e. heart rate, blood pressure, and respiratory rate. On the contrary, stimulating music has been found to initiate sympathetic nervous system activity. This is thought to occur by either a reflexive brainstem response or stimulus interpretation by the amygdala.
ContributorsFlores, Catalina Nicole (Author) / Redding, Kevin (Thesis director) / Hoffer, Julie (Committee member) / Neisewander, Janet (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Abstract White matter thickness correlates with various mental illness. Commissure white matter tracts are responsible for interconnecting the same cortical area in both hemispheres. Injury to the brain can result in thinning and shrinkage even collapsing and detachment of the white matter tracts' myelin sheaths. Injury can affect cognitive function and time points are essential for therapeutic intervention. Research is beginning to identify gradual long-term neurodegenerative effects. With the advancement of brain imaging technology, we know that Wallerian degeneration has a significant negative impact on the white matter tracts throughout the brain (Johnson, Stewart, & Smith, 2013). If major tracts become injured like, the corpus callosum, then it can affect interhemispheric communication. Once myelin is damaged the axon becomes vulnerable, and the mechanisms of nerve recovery are not well known. Myelin sheath recovery has been studied in hopes to proliferate the oligodendrocytes that make up for the atrophied myelin. Neurotoxic chemicals released at activation of macrophages which hinders the brains ability to proliferate myelin protein needed for myelin differentiation adequately. In the central nervous system myelin has mechanisms to recover. Neurogenesis is a naturally occurring recovery mechanism seen after brain injury. Understanding the time points in which brain recovery occurs is important for treatment of diffuse injuries that cannot be identified through some imaging techniques. To better understand critical timepoints of natural recovery after brain injury can allow further investigation for early intervention to promote adequate recovery.
ContributorsLiptow, Kristen Ashley (Author) / Neisewander, Janet (Thesis director) / Law, L. Matthew (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The goal of my study is to test the overarching hypothesis that art therapy is effective because it targets emotional dysregulation that often accompanies significant health stressors. By reducing the salience of illness-related stressors, art therapy may improve overall mood and recovery, particularly in patients with cancer. After consulting the primary literature and review papers to develop psychological and neural mechanisms at work in art therapy, I created a hypothetical experimental procedure to test these hypotheses to explain why art therapy is helpful to patients with chronic illness. Studies found that art therapy stimulates activity of multiple brain regions involved in memory retrieval and the arousal of emotions. I hypothesize that patients with chronic illness have a reduced capacity for emotion regulation, or difficulty recognizing, expressing or altering illness-related emotions (Gross & Barrett, 2011). Further I hypothesize that art therapy improves mood and therapeutic outcomes by acting on the emotion-processing regions of the limbic system, and thereby facilitating the healthy expression of emotion, emotional processing, and reappraisal. More mechanistically, I propose art therapy reduces the perception or salience of stressors by reducing amygdala activity leading to decreased activation of the hypothalamic-pituitary-adrenal (HPA) axis. The art therapy literature and my hypothesis about its mechanisms of action became the basis of my proposed study. To assess the effectiveness of art therapy in alleviating symptoms of chronic disease, I am specifically targeting patients with cancer who exhibit a lack of emotional regulation. Saliva is collected 3 times a week on the day of intervention: morning after waking, afternoon, and evening. Stress levels are tested using one-hour art therapy sessions over the course of 3 months. The Perceived Stress Scale (PSS) assesses an individual's perceived stress and feelings in past and present situations, for the control and intervention group. To measure improvement in overall mood, 10 one-hour art sessions are performed on patients over 10 weeks. A one-hour discussion analyzing the participants' artwork follows each art session. The Spielberger State-Trait Anxiety Inventory (STAI) assesses overall mood for the intervention and control groups. I created rationale and predictions based on the intended results of each experiment.
ContributorsAluri, Bineetha C. (Author) / Orchinik, Miles (Thesis director) / Davis, Mary (Committee member) / Essary, Alison (Committee member) / School of Life Sciences (Contributor) / School for the Science of Health Care Delivery (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05