Browsing by Subject "Alcohol relapse"

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    Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats
    (Elsevier B.V., 2012-02) Dhaher, Ronnie; Toalston, Jamie E.; Hauser, Sheketha R.; Bell, Richard L.; McKinzie, David L.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of Medicine
    Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1–10 mg/kg, subcutaneously [s.c.]; n = 8/dose), LY255582 (LY; 0.03–1 mg/kg, s.c.; n = 8/dose), or vehicle were injected 30 min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors.
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    Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse
    (Wiley, 2015-08) Froehlich, Janice C.; Hausauer, Brett; Fischer, Stephen; Wise, Bradley; Rasmussen, Dennis D.; Department of Medicine, IU School of Medicine
    BACKGROUND: Many alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the "alcohol deprivation effect" or "ADE" and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference ("P" rats). This study explores whether prazosin prevents alcohol "relapse" in P rats, as reflected by a reduced or abolished ADE. METHODS: Adult male P rats were given 24-hour access to food and water and scheduled access to alcohol (15 and 30% v/v solutions presented concurrently) for 2 h/d. After 5 weeks, rats underwent imposed alcohol deprivation for 2 weeks, followed by alcohol reaccess for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected with prazosin (0, 0.5, 1.0, or 2.0 mg/kg body weight, intraperitoneally) once a day for the first 5 days of each alcohol reaccess cycle. RESULTS: Alcohol intake increased on the first day of each alcohol reaccess cycle, demonstrating the formation of an ADE. The ADE was short-lived, lasting only 1 day, during each of the 3 cycles. Prazosin, in all doses tested, prevented the expression of an ADE in all 3 alcohol reaccess cycles. CONCLUSIONS: Prazosin decreases alcohol intake in P rats even in a situation that would be expected to increase alcohol drinking, namely following periods of alcohol deprivation. This suggests that prazosin may be effective in reducing alcohol relapse that often occurs during attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics and heavy drinkers.