The overall goal of this research program is to utilize electrophysiological measures, specifically waking EEG, event-related potentials (ERPs), and measures of sleep EEG to explore the neural substrates which underlie alcohol's abuse liability. Studies in both human and animal models suggest that factors such as: a low level of response to alcohol, anxiety traits, and cognitive/personality variables can moderate risk for the development of alcoholism in humans and perhaps also influence alcohol preference in animals. In addition to these genetic/familial risk factors, individuals must be exposed to periods of heavy drinking to actually develop alcohol use disorders. Heavy drinking can cause persistent neuroadaptive changes in neurochemistry, electrophysiology, and behaviors which contribute to the addiction process. Thus, it is our hypothesis that preexisting genetically influenced risk factors interact with the neuroadaptive changes that occur following chronic alcohol exposure to produce the final outcome we define as the alcoholism phenotype. We have developed well defined animal """"""""correlates"""""""" of human electrophysiological measures associated with alcoholism such as the P300 component of the ERP. Electrophysiological studies have been conducted in outbred strains as well as ethanol preferring (P) and non-preferring (NP) rats in order to characterize genetically influenced variables in an animal model of voluntary ethanol consumption. The current proposal includes an evaluation of replicate lines of high alcohol drinking (HAD1, HAD2) and low alcohol drinking (LAD 1, LAD 2) rats, as well as replicate lines of mouse strains that differ in ethanol consumption (LAP 1, LAP 2, HAP 1,HAP 2). The newly proposed studies will also use electrophysiological measures to further the functional activity of specific brain sites, such as the extended amygdala, during ethanol consumption. Neuropharmacological studies will be aimed at further understanding neuropeptide modulation of alcohol consumption as well as the effects of ethanol exposure on measures of electrophysiology and alcohol consumption. The use of these electrophysiological measures, combined with neurochemical findings will provide data necessary to directly link these peptidergic systems to alcohol preference and long term neuroadaptation to alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006059-15
Application #
6629550
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Egli, Mark
Project Start
1984-01-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
15
Fiscal Year
2003
Total Cost
$370,400
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Sanchez-Alavez, Manuel; Wills, Derek N; Amodeo, Leslie et al. (2018) Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. Alcohol Clin Exp Res 42:624-633
Sanchez-Alavez, Manuel; Nguyen, William; Mori, Simone et al. (2018) Time course of microglia activation and brain and blood cytokine/chemokine levels following chronic ethanol exposure and protracted withdrawal in rats. Alcohol 76:37-45
Amodeo, Leslie R; Wills, Derek N; Sanchez-Alavez, Manuel et al. (2018) Intermittent voluntary ethanol consumption combined with ethanol vapor exposure during adolescence increases drinking and alters other behaviors in adulthood in female and male rats. Alcohol 73:57-66
Ehlers, Cindy L; Sanchez-Alavez, Manuel; Wills, Derek (2018) Effect of gabapentin on sleep and delta and theta EEG power in adult rats exposed to chronic intermittent ethanol vapor and protracted withdrawal during adolescence. Psychopharmacology (Berl) 235:1783-1791
Amodeo, Leslie R; Wills, Derek N; Ehlers, Cindy L (2017) Acute low-level alcohol consumption reduces phase locking of event-related oscillations in rodents. Behav Brain Res 330:25-29
Amodeo, Leslie R; Kneiber, Diana; Wills, Derek N et al. (2017) Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats. Alcohol 59:43-51
Sanchez-Alavez, Manuel; Ehlers, Cindy L (2016) Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis. Int J Psychophysiol 103:53-61
Ehlers, Cindy L; Desikan, Anita; Wills, Derek N (2014) Event-related potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats. Alcohol Clin Exp Res 38:749-59
Desikan, Anita; Wills, Derek N; Ehlers, Cindy L (2014) Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test. Pharmacol Biochem Behav 122:279-85
Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N et al. (2014) Cholinergic modulation of event-related oscillations (ERO). Brain Res 1559:11-25

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