Examination of Cortical/Thalamic-Striatal Circuitry in Modulating Sensitivity to Alcohol and Relapse Public Deposited

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  • March 20, 2019
Creator
  • Jaramillo, Anel
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • All drugs of abuse produce unique interoceptive/subjective (i.e., discriminative stimulus) effects that can impact drug-taking, seeking, and relapse in both clinical and pre-clinical studies. However, the neural circuitry modulating the interoceptive effects of alcohol has yet to be established. The nucleus accumbens core (AcbC), a region known to modulate alcohol-related behaviors, also plays a central role in modulating the discriminative stimulus effects of alcohol. Thus, by investigating the insular cortex (IC) and rhomboid thalamic nucleus (Rh), two brain regions with projections to the AcbC, the experiments in this dissertation sought to investigate the circuitry underlying alcohol-induced interoceptive states and how those internal cues can modulate alcohol-seeking and relapse-like drinking. The IC is implicated in processing interoceptive cues and responding to alcohol-related cues, although its functional role in modulating alcohol-induced interoceptive effects has not been investigated to date. The Rh is proposed to modulate inhibition, behavior flexibility, and motivation, but the role of Rh in modulating any drug-related behaviors has yet to be determined. Utilizing an alcohol discrimination task, pharmacological inhibition of the IC or Rh produced partial alcohol-like effects. Furthermore chemogenetic silencing of the IC or Rh and specific silencing of the IC or Rh outgoing projections to the AcbC potentiated the interoceptive effects of alcohol. Interestingly, in a model of moderate alcohol self-administration, chemogenetic silencing of all IC and Rh outgoing projections did not affect maintenance or reinstatement of alcohol self-administration or the alcohol loading dose effect. However, chemogenetic silencing of IC to AcbC projections decreased alcohol self-administration and increased sensitivity to an alcohol loading dose (i.e., satiation), resulting in attenuated maintenance and reinstatement of alcohol self-administration. Interestingly chemogenetic silencing of the IC outgoing projections and specific IC to AcbC projections did not affect ongoing sucrose self-administration, but did affect relapse-like behavior. Overall, results from the studies within the present dissertation provide a novel role for the insular/thalamic-striatal circuit in modulating sensitivity to alcohol and implicate the insular-striatal circuit in modulating the alcohol-reinforced behavior, while demonstrating the complex role of interoceptive effects in modulating on alcohol-related behaviors.
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  • In Copyright
Advisor
  • Knapp, Darin
  • Besheer, Joyce
  • Morrow, A. Leslie
  • Parnell, Scott
  • Kash, Thomas
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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