The overall goal of this Mentored Research Scientist Award (K01) application is to explore the behavioral and pharmacological ramifications of concurrent ethanol and nicotine administration while providing the candidate (Dr. Matthew Ford) with an enriched training environment and a diversified research experience that will serve to nurture his transition to an independent investigator. The candidate will complement already familiar and established self-administration procedures by working closely with the mentor/sponsor (Dr. Kathleen Grant) to establish proficiency in training drug discriminations for single drugs and drug mixtures. In addition to learning the theory behind the drug discrimination procedure, the concepts of associative blocking and overshadowing will be directly studied in relation to ethanol and nicotine interactions in the generation of a conditioned drug cue. The candidate will also become familiar with several pharmacological strategies that are commonly employed to evaluate the salience and characteristics of a discriminative drug cue, such as, generalization testing and dose-response curve assessments. The sponsor will also guide the candidate in the practice of data analysis, data interpretation and the identification of procedural limitations as specifically related to the drug discrimination procedure. The proposed studies will test specific aims that address the influence of nicotine exposure history and dose on ethanol selfadministration outcomes and evaluate the impact of nicotine on the stimulus control exhibited by an interceptive ethanol cue. This mentored training opportunity will permit the candidate to accumulate additional research skills and experience in neuropharmacological and behavioral approaches to studying alcohol and other abused drugs, and will cement a solid foundation on which to stand as an independent principal investigator. Relevance: An estimated 90% of alcoholics engage in smoking behavior. Through the investigation of concurrent nicotine and ethanol administration, this research application seeks to arrive at a more complete understanding of the functional interactions between nicotine and ethanol. This investigational approach will provide valuable insights into the prevalence of their co-abuse liability, with the added potential to identify treatment strategies for ethanol and nicotine co-dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AA016849-05
Application #
8107690
Study Section
Special Emphasis Panel (ZAA1-DD (81))
Program Officer
Grakalic, Ivana
Project Start
2007-07-05
Project End
2012-12-30
Budget Start
2011-07-01
Budget End
2012-12-30
Support Year
5
Fiscal Year
2011
Total Cost
$123,038
Indirect Cost
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Ramaker, Marcia J; Strong-Kaufman, Moriah N; Ford, Matthew M et al. (2015) Effect of nucleus accumbens shell infusions of ganaxolone or gaboxadol on ethanol consumption in mice. Psychopharmacology (Berl) 232:1415-26
Tanchuck-Nipper, Michelle A; Ford, Matthew M; Hertzberg, Anna et al. (2015) Sex Differences in Ethanol's Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice with a Null Mutation of the 5?-Reductase Type 1 Gene. Behav Genet 45:354-67
Ford, Matthew M; Nickel, Jeffrey D; Kaufman, Moriah N et al. (2015) Null mutation of 5?-reductase type I gene alters ethanol consumption patterns in a sex-dependent manner. Behav Genet 45:341-53
Snelling, Christopher; Tanchuck-Nipper, Michelle A; Ford, Matthew M et al. (2014) Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure-Prone and -Resistant mice during chronic ethanol withdrawal. Psychopharmacology (Berl) 231:3401-14
Ramaker, M J; Ford, M M; Phillips, T J et al. (2014) Differences in the reinstatement of ethanol seeking with ganaxolone and gaboxadol. Neuroscience 272:180-7
Ford, Matthew M (2014) Applications of schedule-induced polydipsia in rodents for the study of an excessive ethanol intake phenotype. Alcohol 48:265-76
Ford, Matthew M; Steele, Andrea M; McCracken, Aubrey D et al. (2013) The relationship between adjunctive drinking, blood ethanol concentration and plasma corticosterone across fixed-time intervals of food delivery in two inbred mouse strains. Psychoneuroendocrinology 38:2598-610
Ford, Matthew M; Davis, Natalie L; McCracken, Aubrey D et al. (2013) Contribution of NMDA glutamate and nicotinic acetylcholine receptor mechanisms in the discrimination of ethanol-nicotine mixtures. Behav Pharmacol 24:617-22
Shabani, Shkelzen; Dobbs, Lauren K; Ford, Matthew M et al. (2012) A genetic animal model of differential sensitivity to methamphetamine reinforcement. Neuropharmacology 62:2169-77
Ramaker, Marcia J; Strong, Moriah N; Ford, Matthew M et al. (2012) Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration. Neuropharmacology 63:555-64

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