This K99/R00 career development award proposal (Intersection of Pain and Ethanol-Seeking Mechanisms in Ethanol Dependence) incorporates themes related to neuronal mechanisms I have investigated in the past, including the regulation of in vivo intracellular signaling and compulsive drug taking and drug-seeking behaviors, using models of drug dependence in rats. These studies were conducted with the support of individual NRSA awards at both pre- and postdoctoral levels.
The aim of this proposal is to incorporate new training in neurochemistry (in vivo microdialysis) and nociceptive behavioral techniques, and to integrate the use of a comparative species (mice), to complement and enrich this background. I feel that this combination of new techniques (learned during the K99 phase) applied to the investigation of pain and ethanol-seeking behaviors will provide valuable insight into alcohol dependence, and, when combined with the personalized mentoring provided by Drs. Parsons and Koob within an environment as rich as The Scripps Research Institute, will greatly facilitate my transition to an independent research career during the R00 phase. The research development plan is conducted in accordance with the TSRI postdoctoral office's Individual Development Plan (IDP) program, and includes specialized training elements serving both immediate and long-term goals related to such topics as grantsmanship, effective scientific communication, and ethics. The main research objective of the current proposal is to investigate the convergence of central nociceptive and ethanol-seeking biobehavioral mechanisms in promoting and/or maintaining the ethanol-dependent state. Based on previous data from both pain- and ethanol-related fields, I hypothesize a specific role for increased endogenous cannabinoid activity and associated MAP kinase signaling potentiation in the anterior cingulate cortex in mediating this intersection, and further hypothesize that chronic pain states facilitate the transition from ethanol use to dependence via this mechanism. I propose an innovative experimental strategy that combines highly relevant behavioral techniques with comparative in vivo measures of neurotransmitter levels and intracellular signaling spanning from the extracellular space to the nucleus, including measures of both pre- and postsynaptic protein phosphorylation. Experiments conducted during the R00 phase will build on K99 phase work, and should provide a substantial base for my future investigations into the biobehavioral mechanisms of alcohol dependence. A better understanding of the relationship between chronic ethanol exposure, altered nociception, and compulsive ethanol seeking will provide further insight into mechanisms underlying the transition from recreational alcohol use to alcoholism, as well as reveal new treatment opportunities.

Public Health Relevance

Individuals suffering from chronic pain may be more vulnerable to develop alcohol dependence and use alcohol to treat pain symptoms. This project will examine overlapping brain biochemical mechanisms of pain and alcoholism that contribute to the worsening and potential interdependence of these two disorders, with the ultimate goal of developing better therapeutic strategies for these devastating conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Transition Award (R00)
Project #
5R00AA020839-05
Application #
8918260
Study Section
Special Emphasis Panel (NSS)
Program Officer
Liu, Qi-Ying
Project Start
2014-09-01
Project End
2017-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Avegno, Elizabeth M; Lobell, Thomas D; Itoga, Christy A et al. (2018) Central Amygdala Circuits Mediate Hyperalgesia in Alcohol-Dependent Rats. J Neurosci 38:7761-7773
Pahng, Amanda R; Edwards, Scott (2018) Measuring Pain Avoidance-Like Behavior in Drug-Dependent Rats. Curr Protoc Neurosci 85:e53
Pahng, Amanda R; Paulsen, Rod I; McGinn, M Adrienne et al. (2018) Dysregulation of c-Jun N-terminal kinase phosphorylation in alcohol dependence. Alcohol 75:11-18
Pahng, Amanda R; McGinn, M Adrienne; Paulsen, Rod I et al. (2017) The Prefrontal Cortex as a Critical Gate of Negative Affect and Motivation in Alcohol Use Disorder. Curr Opin Behav Sci 13:139-143
Mayeux, Jacques; Katz, Paige; Edwards, Scott et al. (2017) Inhibition of Endocannabinoid Degradation Improves Outcomes from Mild Traumatic Brain Injury: A Mechanistic Role for Synaptic Hyperexcitability. J Neurotrauma 34:436-443
Pahng, Amanda R; Paulsen, Rod I; McGinn, M Adrienne et al. (2017) Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent and Non-Dependent Rats. Neuroscience 366:1-14
Whitaker, Annie M; Farooq, Muhammad A; Edwards, Scott et al. (2016) Post-traumatic stress avoidance is attenuated by corticosterone and associated with brain levels of steroid receptor co-activator-1 in rats. Stress 19:69-77
Edwards, Scott (2016) Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder. Prog Brain Res 223:63-76
McGinn, M Adrienne; Paulsen, Rod I; Itoga, Christy A et al. (2016) Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1 Phosphorylation. Alcohol Clin Exp Res 40:2537-2547
Somkuwar, Sucharita S; Fannon, McKenzie J; Staples, Miranda C et al. (2016) Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling. Brain Struct Funct 221:4319-4335

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