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 #
5R01AA004200-06
Application #
3108889
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1985-09-27
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
6
Fiscal Year
1986
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
McMillen, Brian A; Joyner, Paul W; Parmar, Chandresh A et al. (2004) Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption of ethanol by a genetic drinking rat. Brain Res Bull 64:279-84
Mega, Benjamin T; Sheppard, Katherine W; Williams, Helen L et al. (2002) On the role of monoamine oxidase-A for the maintenance of the volitional consumption of ethanol in two different rat models. Naunyn Schmiedebergs Arch Pharmacol 366:319-26
West, M W; Biggs, T A; Schreiber, R et al. (1999) Calcium channel agonist (-)-BAY k 8644 suppresses free and limited access intake of alcohol in genetic drinking rats. Psychopharmacology (Berl) 142:261-9
Myers, R D; Robinson, D E (1999) Tetrahydropapaveroline injected in the ventral tegmental area shifts dopamine efflux differentially in the shell and core of nucleus accumbens in high-ethanol-preferring (HEP) rats. Alcohol 18:83-90
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
Simpson, C W; Resch, G E; Millington, W R et al. (1998) Glycyl-L-glutamine injected centrally suppresses alcohol drinking in P rats. Alcohol 16:101-7
McMillen, B A; Means, L W; Matthews, J N (1998) Comparison of the alcohol-preferring P rat to the Wistar rat in behavioral tests of impulsivity and anxiety. Physiol Behav 63:371-5
Myers, R D; Adell, A; Lankford, M F (1998) Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain of rats: a critical review. Neurosci Biobehav Rev 22:371-87
McMillen, B A; Williams, H L (1998) Role of taste and calories in the selection of ethanol by C57BL/6NHsd and Hsd:ICR mice. Alcohol 15:193-8

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