The present proposal represents a collaborative effort between investigators in the fields of alcohol pharmacology and gustatory neurobiology to systematically examine the contribution of gustatory receptor and central neural circuits processing appetitive oral alcohol information to genetically-mediated alcohol preference. Although significant progress has been made in identifying the biological mechanisms that mediate alcohol reinforcement and contribute to its consumption, our understanding of the complex neuroanatomical circuits that control initiation and maintenance of oral alcohol ingestion is far from complete. A substantial body of evidence from animal and human studies over the last decade has supported a robust genetically-influenced relationship between the ingestion of alcohol and consumption of naturally-reinforcing sweet substances, but the mechanisms underlying inherited co-variation in alcohol and sweet intake are presently unknown. Recent findings from our laboratory have shown that oral alcohol stimulation potently activates sweet-responsive gustatory circuits in the nucleus of the solitary tract and that alcohol-induced activity in these pathways is directly inhibited by pharmacological blockade of oral sweet receptors. New preliminary behavioral data indicate that genetic deletion of the T1r3 sweet taste receptor in mice produces indifference to alcohol in long-term intake tests at concentrations that are normally highly preferred. Experiments under Specific Aim 1 will measure the neurophysiological processing of ethanol gustatory information in the NST across multiple selectively bred alcohol-preferring/-nonpreferring rat lines and their nonselected progenitor lines to test the hypothesis that enhanced alcohol-induced activation of central sweet taste circuits is a consistent biological phenotype associated with genetically-mediated alcohol preference. Experiments under Specific Aim 2 will examine the effects of gustatory sweet receptor blockade on psychophysical orosensory responses to ethanol in alcohol- and sweet-preferring P, HAD1, HAD2, and C57BL lines/strains and their respective nonpreferring/nonselected lines to test the hypothesis that reduction of oral alcohol stimulation of sweet taste pathways will decrease orosensory-mediated ethanol preference. At the conclusion of this project, we will have produced a body of valuable data addressing the specific contribution of gustatory receptor and central neural pathways conveying appetitive oral alcohol information to genetically-influenced ethanol preference. More generally, these studies will enhance our understanding of the central nervous system processing of alcohol sensory information, an area that is currently not well understood.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Gentry, Thomas
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San Diego State University
Schools of Arts and Sciences
San Diego
United States
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Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma et al. (2015) Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats. PLoS One 10:e0139012
Brasser, Susan M; Castro, Norma; Feretic, Brian (2015) Alcohol sensory processing and its relevance for ingestion. Physiol Behav 148:65-70
Brasser, Susan M; Silbaugh, Bryant C; Ketchum, Myles J et al. (2012) Chemosensory responsiveness to ethanol and its individual sensory components in alcohol-preferring, alcohol-nonpreferring and genetically heterogeneous rats. Addict Biol 17:423-36
Lemon, Christian H; Wilson, David M; Brasser, Susan M (2011) Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats. J Neurophysiol 106:3145-56
Brasser, Susan M; Norman, Meghan B; Lemon, Christian H (2010) T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference. Physiol Genomics :
Ellingson, Jarrod M; Silbaugh, Bryant C; Brasser, Susan M (2009) Reduced oral ethanol avoidance in mice lacking transient receptor potential channel vanilloid receptor 1. Behav Genet 39:62-72