This application is a request to support ongoing projects in different stages of completion as well as those to be initiated. The principal objectives and specific aims of this research program during the proposed grant period (-05 through -08 years) are summarized as follows: First, studies will continue on the anatomical localization of specific sites in the brain which are selectively reactive to an amine-aldehyde condensation product or other neuroactive substance in terms of its mediation of a shift in alcohol self-selection. One structure thus far identified which mediates tetrahydropapaveroline (THP) - induced drinking of alcohol is the hippocampus. Experiments are being extended on the acute effect of different doses and volumes of alkaloid infusion as well as the regimen of chronic delivery to a site by means of an osmotic mini-pump. The anatomical structures include the nucleus reticularis paragigantocellularis (NRPG), periaqueductal gray (PAG), nucleus accumbens (NAC), ventromedial hypothalamus (VMH), and dorsal, ventral and other areas of the hippocampus. Second, systematic investigations will continue in which the attempt is made to either elevate alcohol drinking or attenuate it pharmacologically. Opiate receptor antagonists, an aldehyde dehydrogenase inhibitor, benzodiazepine receptor agonist or antagonist as well as other substances are administered directly into the brain to determine whether volitional alcohol intake can be modified in the test animal. Third, """"""""push-pull"""""""" perfusion procedures will be used for examining and characterizing in vivo chemical activity of circumscribed regions of the brain of the alcohol dependent animal. The kinetics of release of monoamines and their metabolites will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA004200-05A1
Application #
3108885
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1985-09-27
Project End
1989-08-31
Budget Start
1985-09-27
Budget End
1986-08-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Myers, R D; Robinson, D E (1999) Mmu and D2 receptor antisense oligonucleotides injected in nucleus accumbens suppress high alcohol intake in genetic drinking HEP rats. Alcohol 18:225-33
Jones, E A; McMillen, B A (1999) The cardiovascular effects of amperozide: interactions with cocaine. Pharmacol Toxicol 84:53-8
West, M W; Kalmus, G; Myers, R D (1998) Limited access to ethanol in genetic drinking rats is suppressed while feeding is enhanced by the mixed 5-HT1A agonist/5-HT2A antagonist FG5938. Pharmacol Biochem Behav 60:823-8
West, M W; Biggs, T A; Tavares, E et al. (1998) Drinking patterns in genetic low-alcohol-drinking (LAD) rats after systemic cyanamide and cerebral injections of THP or 6-OHDA. Alcohol 15:239-47
Wilcox, R E; McMillen, B A (1998) The rational use of drugs as therapeutic agents for the treatment of the alcoholisms. Alcohol 15:161-77
Myers, R D; Robinson, D E; West, M W et al. (1998) Genetics of alcoholism: rapid development of a new high-ethanol-preferring (HEP) strain of female and male rats. Alcohol 16:343-57

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