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Mechanoreceptor Activation In The Treatment Of Drug-Use Disorders: Mechanism And Outcome, Kyle Bills

Theses and Dissertations

The therapeutic benefits attributed to activation of peripheral mechanoreceptors are poorly understood. There is growing evidence that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) that are outside the canonical somatosensory circuits. This work demonstrates that activation of peripheral mechnoreceptors via mechanical stimulation (MStim) is sufficient to increase dopamine release in the nucleus accumbens (NAc), alter neuron firing rate in the ventral tegmental area (VTA) and increase membrane translocation of delta opioid receptors (DORs) in the NAc. Further, we demonstrate that these effects are dependent on DORs and acetylcholine receptors. Additionally, MStim can block neuronal markers of …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Baked And Buzzed: Investigating The Influence Of Co-Use Of Cannabis And Alcohol On White Matter Integrity In Emerging Adults, Natasha E. Wright

Theses and Dissertations

Objective: Growing evidence suggests alcohol and cannabis use independently alter neural structure and functioning, particularly during sensitive developmental time periods such as adolescence and emerging adulthood. However, there has been minimal investigation into the effects co-occurring use of these two substances, despite preliminary evidence of unique acute and psychopharmacological changes due to using alcohol and cannabis together.

Method: Data drawn from the IDEAA Consortium was utilized to assess white matter integrity as measured by FreeSurfer’s TRACULA in emerging adults (n=192; 16-27 years old). Timeline Follow-Back was used to calculate past month cannabis use, alcohol use, co-use days, binge alcohol episode, …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

The Role Of Connexin-36 Gap Junctions In Alcohol Intoxication And Reward, Kathryn Diane Bradley

Theses and Dissertations

The purpose of this thesis project was to examine the function of connexin-36 (Cx36) gap junctions (GJs) in producing alcohol's intoxicating and rewarding effects. GABA neurons are thought to inhibit dopamine (DA) neurotransmission in the mesocorticolimbic system, which originates in the midbrain ventral tegmental area (VTA) and projects to limbic structures such as the nucleus accumbens (NAcc). The mesolimbic DA system is believed to be the neural substrate of alcohol intoxication and addiction (Tepper, Paladini, & Celada, 1998). Alcohol suppresses the firing rate of GABA neurons in the VTA (Gallegos, Criado, Lee, Henriksen, & Steffensen, 1999) and presumably disinhibits DA …

Neuronal And Molecular Adaptations Of Gaba Neurons In The Ventral Tegmental Area To Chronic Alcohol, Kimberly Hales

Theses and Dissertations

The purpose of this thesis project was to examine the effects of chronic alcohol on the excitability and molecular adaptation of GABA neurons of the ventral tegmental area (VTA). GABA neurons are of interest with regards to ethanol intoxication, reinforcement, and dependence due to their widespread distribution and connectivity to mesocorticolimbic dopamine (DA) neurons implicated in alcohol reward and addiction. Since we have previously shown adaptation of VTA GABA neuron firing rate to chronic ethanol (Gallegos, Criado et al. 1999) and suppression of gap-junction (GJ) mediated coupling between these neurons by acute ethanol (Stobbs, Ohran et al. 2004), we wanted …