Research Interests

My primary research interests are directed at the neurobiology of alcoholism. A growing body of literature shows that central neuropeptides, including those involved in the integrating emotional and appetitive behaviors, regulate neurobiological responses to ethanol. The overarching goal of the research conducted in my laboratory is to discover the roles that central neuropeptides play in modulating excessive ethanol consumption. Specifically, my research aims to:

• Determine the roles that central neuropeptides play in modulating ethanol consumption, binge-like ethanol drinking, and the reinforcing properties of ethanol.
• Indentify the central neurochemical pathways that modulate the effects of psychological stress on excessive ethanol drinking.
• Determine how neuropeptides interact with each other and with intracellular signaling mechanisms (such as cAMP-dependent protein kinase A; PKA) in the modulation of excessive ethanol consumption.
  
  

Research Contributions

Discovery that ethanol consumption is inversely related to neuropeptide Y (NPY) signaling:

• NPY signaling modulates ethanol consumption via the Y1 and Y2 receptors.
• NPY signaling protects against elevated levels of anxiety-like behavior stemming from ethanol withdrawal.

Discovered that ethanol consumption is modulated by the hypothalamic melanocortin (MC) system:

• MC receptor agonists reduce, and MC receptor antagonists increase, ethanol consumption by mice, respectively.
• MCs modulate ethanol consumption via the MC-4 receptor.
• The endogenous MC receptor antagonist, agouti-related protein (AgRP), modulates ethanol consumption and the reinforcing properties of ethanol, and promotes binge-like ethanol drinking in mice.
• Chronic exposure to ethanol promotes reductions of the endogenous MC neuropeptide, α-MSH, in specific regions of the rat brain.

Discovered novel roles for corticotropin releasing factor (CRF) in modulating neurobiological responses to ethanol:

• Binge-like ethanol drinking in mice is modulated by CRF-1 receptor signaling.
• The delayed increase of ethanol drinking by mice exposed to psychological stress is modulated by CRF-1 receptor signaling.
• CRF-1 receptor signaling modulates the expression of sensitization to the locomotor stimulant effects of ethanol stemming from repeated ethanol administrations in mice.

Discovered the RIIβ subunit of PKA modulates neurobiological responses to ethanol:

• Deletion of the RIIβ subunit of PKA in mice is associated with increased consumption of ethanol and reduced sensitivity to the sedative properties of this drug.
• Mice lacking the RIIβ subunit of PKA show increased sensitivity to the locomotor stimulant effects of ethanol and behavioral sensitization stemming from repeated ethanol injections.
  
  

Current Research Projects

The Role of Neuropeptide Y (NPY) in Uncontrolled Ethanol Drinking and Relapse Behavior Resulting from Exposure to Stressful Stimuli.  Supported by the Department of Defense (W81XWH-06-1-0158); Thiele (PI).

Melanocortin Neuropeptides and Ethanol Intake. Supported by the National Institute on Alcohol Abuse and Alcoholism (R01-AA015148); Thiele (PI).

The Role of Neuropeptide Y in Ethanol Intake and Sensitivity. Supported by the National Institute on Alcohol Abuse and Alcoholism (R01-AA013573); Thiele (PI).

Melanocortin and Opioid Peptide Interactions in the Modulation of Binge Ethanol Drinking. Supported by the Department of Defense (W81XWH-09-1-0293); Thiele (PI).

Current Mentored Research Projects

Stress-Induced Increases of Ethanol Intake: The Role of Neuropeptide Y (NPY). (F31-AA017818); Angela Lyons (PI), Thiele (Mentor).

CRF Signaling in Stress- and Dependence-induced ethanol consumption. (F31-AA017803); Emily Lowery (PI), Thiele (Mentor).