Browsing by Author "Fischer, Stephen M."

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    Alcohol Drinking and Blood Alcohol Concentration Revisited
    (Wiley, 2017) Dilley, Julian E.; Nicholson, Emily; Fischer, Stephen M.; Zimmer, Robin; Froehlich, Janice C.; Medicine, School of Medicine
    Background It is widely assumed that the amount of alcohol in the blood reflects the amount of alcohol consumed. However, several factors in addition to amount of alcohol consumed can influence blood alcohol concentration (BAC). This study examines the effect of alcohol dose, concentration, and volume on BAC in rats with a high-alcohol-drinking (HAD) phenotype. Methods Study 1 examined the relationship between the amount of alcohol consumed and BAC. Alcohol-naïve, male, HAD rats (N = 7) were given access to alcohol for 2 h/d for 9 consecutive days with food and water ad libitum. Alcohol intake and BAC were measured at 30, 60, and 90 minutes after onset of access. Study 2 examined the effects of altering alcohol dose, concentration, and volume on BAC (as measured by area under the curve). Alcohol-naïve, male, HAD rats (N = 39) were infused, via an intragastric cannulus, with 1.16, 2.44, or 3.38 g alcohol/kg body weight (BW), produced by varying alcohol volume while holding concentration constant or by holding volume constant while varying concentration. Other rats were infused with 10, 15, or 20% v/v alcohol solutions while holding dose constant. Results BAC was more strongly correlated with the ratio of alcohol intake (g/kg BW) to total fluid intake (mls) (R = 0.85 to 0.97, p < 0.05 to p < 0.001) than it was with the amount of alcohol consumed (g/kg BW) (R = 0.70 to 0.81, p < 0.05). No effect of alcohol dose was seen during the first hour following the onset of an alcohol infusion regardless of whether dose was achieved by altering alcohol volume or concentration. After 1 hour, higher alcohol doses were predictive of greater BACs. Conclusions The fact that a 3-fold difference in alcohol dose did not result in significant differences in BACs during the first 30 minutes after ingestion of alcohol has potentially important implications for interpretation of studies that measure alcohol-sensitive end points during this time.
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    Combining varenicline (Chantix) with naltrexone decreases alcohol drinking more effectively than does either drug alone in a rodent model of alcoholism
    (Wiley, 2016-09) Froehlich, Janice C.; Fischer, Stephen M.; Dilley, Julian E.; Nicholson, Emily; Smith, Teal; Filosa, Nick; Rademacher, Logan; Cellular and Integrative Physiology, School of Medicine
    Background This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol experienced P rats that had been drinking alcohol (15% v/v) for 2 hrs/day for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0 or 2.0 mg/kg BW), NTX alone (10.0, 15.0 or 20.0 mg/kg BW) or VAR + NTX in one of four dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side-effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.
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    Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism
    (Wiley, 2016-09) Froehlich, Janice C.; Fischer, Stephen M.; Dilley, Julian E.; Nicholson, Emily; Smith, Teal; Filosa, Nick; Rademacher, Logan; Department of Medicine, IU School of Medicine
    Background This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol-experienced P rats that had been drinking alcohol (15% v/v) for 2 h/d for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0, or 2.0 mg/kg body weight [BW]), NTX alone (10.0, 15.0, or 20.0 mg/kg BW), or VAR + NTX in 1 of 4 dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days, and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.