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Ethanol metabolism in short and long sleep mice: Dose-response relations
TENTH NORTH CAROLINA ABSTRACTS
ANALYSIS OF A CHANGE IN DISTILLED SPIRITS AVAILABILITY IN N.C. AND ITS IMPACT ON ALCOHOLISM PROBLEMS. H.D. Holder~ The Human Ecology Institute, Chapel Hill, N.C. 27514. In 1978 N.C. enacted a change in the law to permit liquorby-the-drink (LBD) for the first time since prohibition. This project utilizes this as a natural experiment to test hypotheses concerning statistically significant impact on alcoholism and problem drinking resulting from this change in distilled spirits availability. This change from "brown bagging" to LBD produced an important alteration in the type of distilled spirits on-premise outlets. This project employs an interrupted time series quasi-experimental design with switching replications and ARIMA (autoregressive integrated moving average) modelling. Primary measures taken quarterly from 1968 to 1982 include: (a) alcoholism admissions for state and local treatment facilities, (b) cirrhotic mortality rate, and (c) traffic accidents. While studies have shown association between availability, apparent consumption and alcohol-related problems, they often do not provide information about the contribution (if any) of specific types of distilled spirits availabilitx There have been few opportunities to study natural experiments and even fewer studies of liquor-by-the-drink as a possible factor in rates of alcoholism and problem drinking. (Supported by the North Carolina Alcoholism Research Authority Grant #8213.)
PROFILE OF BIOGENIC AMINES, THEIR METABOLITES AND OTHER FACTORS IN THE CSF OF THE ALCOHOL-DRINKING MONKEY. C.O. Harris and R.D. Myers, Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, NC 27514. From studies of Borg and others,, it is known that the normal profile of chemical constituents of CSF is substantially modified as a result of excessive ingestion of alcohol. For example, in the CSF of the alcoholic and non-alcoholic patient, certain monoamine metabolites including MHPG differ considerably. In the present experiments, CSF collected from macaque monkeys which exhibit high or low intakes of alcohol has been examined by methods of HPLC with electrochemical detection. CSF is withdrawn by gravity from the cerebral ventricle, frozen immediately and stored at -70°C. For analysis, it is applied directly onto a C18 ODS-reverse-phase column to identify and quantitate selected neurotransmitters and their metabolites. Since alcohol affects the activity of certain CNS neurotransmitters, CSF assays were conducted before, during and after a period of alcohol drinking. Preliminary resuits show differences in the profile of HPLC record~ with up to seven peaks characterized thus far. Unknown substances eluted from the HPLC column which depend on the condition of the subject will ultimately be characterized. Thus, with the usage of HPLC technology, constituents of the CSF of the human and infra-human primate can be analyzed and monitored with respect to a change induced in the chemical milieu of the brain's internal fluid system. (Supported in part by NIAAA Grant ROI AA 04200 03 and AlIA Grant #8203.)
169
THE ROLE OF INFERIOR COLLICULUS GABA ON ETHANOL WITHDRAWA AUDIOGENIC SEIZURES. T.J.McCown, G.D.Frye and G.R.Breese, Biological Sciences Research Center, U.N.C. School of Medicine, Chapel Hill, N.C. 27514 The inferior colliculi have been implicated in the mediation of ethanol withdrawal audiogenic seizures, so t following studies were conducted in order to assess the r of GABA in the phenomenon. Rats received chronic administ tion of ethanol via a liquid diet regimen for two weeks a then were withdrawn from the ethanol for eight hours. Control rats exhibit wild running, clonus and tonus when subsequently exposed to a 90db bell for up to one minute. However, bilateral microinjection of the putative GABA agonist, muscimol (10-30ng/side) into the inferior collie blocked the auaiogenically-induced seizures. Furthermore, microinjection of GABA (10~g), THIP (300ng) or chlordiaz( poxide (10-20~g) also blocked the ethanol withdrawal audJ genic seizures. Microinjection of 1-3, butanediol had no effect. Conversely, the GABA antagonist, bicuculine, cau~ similar seizures when doses as low as 6ng were microinje( into the inferior colliculi. These studies demonstrate t~ GABA transmission in the inferior colliculi is critical I the expression of ethanol withdrawal audiogenic seizures Thus, hyperexcitability in the CNS during ethanol withdr~ could be due to a functional decrease in GABA transmissi( (This work was supported by Nozth Carolina Alcoholism Research Authority Grant #8207)
ETHANOL METABOLISM IN S H O R T AND LONG SLEEP MIC • a D O S E - R E S P O N S Ea R E L A T I O N S . G.L. McLaushhn, E. Glassman a B.U. Brad for~, R.G. Thurman, Depts. Pharmacology a a Biochemistry, U. of North Carolina, Chapel Hill, NC. The purpose of this study was to study rates of ethanol eli~ nation in long (LS) and short sleep (SS) mice in rive. Basal rat of ethanol elimination were determined following Lp. injection ethanol (0.5 to 3.5 g/kg) by taking multiple breath samples. Mi were also exposed to ethanol vapor for 4 hours in concentratio to achieve blood ethanol levels comparable to those obserw following injection. Blood glucose was also monitored hourly ov 4 h in blood samples taken from the tail. Following injection of up to 2 g/kg ethanol, basal rates ethanol metabolism were similar (ca. 15 g/kg/h) in LS and mice. Higher doses of ethanol had little effect on SS mice, b caused a marked inhibition (50%) in rate in the LS mice. T~ inhibition was associated with a Large (up to 25 m M ) increase blood glucose and sleep. When rates of ethanol elimination determined following yap treatment were compared with rates obtained from experimen where ethanol was injected to give similar blood levels, be strains exhibited a Swift Increase in Alcohol Metabolism (SIA at intermediate blood ethanol levels. In both strains, changes blood glucose correlated well with S I A M (r = 0.77 to 0.~ suggesting that glycogenolytic hormones may be involved in t mecnanLsm of SlAM ( N C A R A #8109).
ANALYSIS OF A CHANGE IN DISTILLED SPIRITS AVAILABILITY IN N.C. AND ITS IMPACT ON ALCOHOLISM PROBLEMS. H.D. Holder~ The Human Ecology Institute, Chapel Hill, N.C. 27514. In 1978 N.C. enacted a change in the law to permit liquorby-the-drink (LBD) for the first time since prohibition. This project utilizes this as a natural experiment to test hypotheses concerning statistically significant impact on alcoholism and problem drinking resulting from this change in distilled spirits availability. This change from "brown bagging" to LBD produced an important alteration in the type of distilled spirits on-premise outlets. This project employs an interrupted time series quasi-experimental design with switching replications and ARIMA (autoregressive integrated moving average) modelling. Primary measures taken quarterly from 1968 to 1982 include: (a) alcoholism admissions for state and local treatment facilities, (b) cirrhotic mortality rate, and (c) traffic accidents. While studies have shown association between availability, apparent consumption and alcohol-related problems, they often do not provide information about the contribution (if any) of specific types of distilled spirits availabilitx There have been few opportunities to study natural experiments and even fewer studies of liquor-by-the-drink as a possible factor in rates of alcoholism and problem drinking. (Supported by the North Carolina Alcoholism Research Authority Grant #8213.)
PROFILE OF BIOGENIC AMINES, THEIR METABOLITES AND OTHER FACTORS IN THE CSF OF THE ALCOHOL-DRINKING MONKEY. C.O. Harris and R.D. Myers, Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, NC 27514. From studies of Borg and others,, it is known that the normal profile of chemical constituents of CSF is substantially modified as a result of excessive ingestion of alcohol. For example, in the CSF of the alcoholic and non-alcoholic patient, certain monoamine metabolites including MHPG differ considerably. In the present experiments, CSF collected from macaque monkeys which exhibit high or low intakes of alcohol has been examined by methods of HPLC with electrochemical detection. CSF is withdrawn by gravity from the cerebral ventricle, frozen immediately and stored at -70°C. For analysis, it is applied directly onto a C18 ODS-reverse-phase column to identify and quantitate selected neurotransmitters and their metabolites. Since alcohol affects the activity of certain CNS neurotransmitters, CSF assays were conducted before, during and after a period of alcohol drinking. Preliminary resuits show differences in the profile of HPLC record~ with up to seven peaks characterized thus far. Unknown substances eluted from the HPLC column which depend on the condition of the subject will ultimately be characterized. Thus, with the usage of HPLC technology, constituents of the CSF of the human and infra-human primate can be analyzed and monitored with respect to a change induced in the chemical milieu of the brain's internal fluid system. (Supported in part by NIAAA Grant ROI AA 04200 03 and AlIA Grant #8203.)
169
THE ROLE OF INFERIOR COLLICULUS GABA ON ETHANOL WITHDRAWA AUDIOGENIC SEIZURES. T.J.McCown, G.D.Frye and G.R.Breese, Biological Sciences Research Center, U.N.C. School of Medicine, Chapel Hill, N.C. 27514 The inferior colliculi have been implicated in the mediation of ethanol withdrawal audiogenic seizures, so t following studies were conducted in order to assess the r of GABA in the phenomenon. Rats received chronic administ tion of ethanol via a liquid diet regimen for two weeks a then were withdrawn from the ethanol for eight hours. Control rats exhibit wild running, clonus and tonus when subsequently exposed to a 90db bell for up to one minute. However, bilateral microinjection of the putative GABA agonist, muscimol (10-30ng/side) into the inferior collie blocked the auaiogenically-induced seizures. Furthermore, microinjection of GABA (10~g), THIP (300ng) or chlordiaz( poxide (10-20~g) also blocked the ethanol withdrawal audJ genic seizures. Microinjection of 1-3, butanediol had no effect. Conversely, the GABA antagonist, bicuculine, cau~ similar seizures when doses as low as 6ng were microinje( into the inferior colliculi. These studies demonstrate t~ GABA transmission in the inferior colliculi is critical I the expression of ethanol withdrawal audiogenic seizures Thus, hyperexcitability in the CNS during ethanol withdr~ could be due to a functional decrease in GABA transmissi( (This work was supported by Nozth Carolina Alcoholism Research Authority Grant #8207)
ETHANOL METABOLISM IN S H O R T AND LONG SLEEP MIC • a D O S E - R E S P O N S Ea R E L A T I O N S . G.L. McLaushhn, E. Glassman a B.U. Brad for~, R.G. Thurman, Depts. Pharmacology a a Biochemistry, U. of North Carolina, Chapel Hill, NC. The purpose of this study was to study rates of ethanol eli~ nation in long (LS) and short sleep (SS) mice in rive. Basal rat of ethanol elimination were determined following Lp. injection ethanol (0.5 to 3.5 g/kg) by taking multiple breath samples. Mi were also exposed to ethanol vapor for 4 hours in concentratio to achieve blood ethanol levels comparable to those obserw following injection. Blood glucose was also monitored hourly ov 4 h in blood samples taken from the tail. Following injection of up to 2 g/kg ethanol, basal rates ethanol metabolism were similar (ca. 15 g/kg/h) in LS and mice. Higher doses of ethanol had little effect on SS mice, b caused a marked inhibition (50%) in rate in the LS mice. T~ inhibition was associated with a Large (up to 25 m M ) increase blood glucose and sleep. When rates of ethanol elimination determined following yap treatment were compared with rates obtained from experimen where ethanol was injected to give similar blood levels, be strains exhibited a Swift Increase in Alcohol Metabolism (SIA at intermediate blood ethanol levels. In both strains, changes blood glucose correlated well with S I A M (r = 0.77 to 0.~ suggesting that glycogenolytic hormones may be involved in t mecnanLsm of SlAM ( N C A R A #8109).