Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse

Abstract

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.

Keywords: Alcohol Deprivation Effect; Alcohol Preferring Rats; Alcohol Relapse; Prazosin.

Fig. 1

Alcohol intake (7 days/week) in P rats given scheduled access to alcohol (15% and 30% v/v) for 14 weeks prior to onset of 3 cycles of alcohol deprivation (D) for 2 weeks followed by 2 weeks of alcohol reaccess (R). Each point represents the mean ± SE.

Fig. 2

Effect of daily prazosin treatment (0, 0.5, 1.0 or 2.0 mg/kg, IP) on 2-hour alcohol intake (g/kg BW) in P rats during the first alcohol reaccess cycle. Prazosin was injected prior to onset of alcohol access on each of the 5 days of alcohol reaccess. Each bar represents the mean ± SE. Predeprivation vs day 1 in the vehicle group = *p<0.05; predeprivation vs day 1 in the 0.5 mg/kg prazosin group = *p<0.05.

Fig. 3

Effect of daily prazosin treatment (0, 0.5, 1.0 or 2.0 mg/kg IP) on 2-hour alcohol intake (g/kg BW) in P rats during the second alcohol reaccess cycle. Prazosin was injected prior to onset of alcohol access on each of the 5 days of alcohol reaccess. Each bar represents the mean ± SE. Predeprivation vs day 1 in the vehicle group = *p<0.05; predeprivation vs day 1 in the 0.5 mg/kg prazosin group = *p<0.05; predeprivation vs day 1 in the 2.0 mg/kg prazosin group = **p < 0.001. Vehicle vs prazosin treatment across all 5 days of alcohol reaccess for 0.5 mg/kg = ^† p < 0.01, for 1.0 mg/kg = ^† p < 0.01, for 2.0 mg.kg =^† p < 0.01.

Fig. 4

Effect of daily prazosin treatment (0, 0.5, 1.0 or 2.0 mg/kg IP) on 2-hour alcohol intake (g/kg BW) in P rats during the third alcohol reaccess cycle. Prazosin was injected prior to onset of alcohol access on each of the 5 days of alcohol reaccess. Each bar represents the mean ± SE. Predeprivation vs. day 1 in the vehicle group = *p<0.05; predeprivation vs day 1 in the 0.5 mg/kg and 1.0 mg/kg BW prazosin groups = **p<0.01. Vehicle vs. prazosin in doses of 0.5mg/kg BW and 1.0 mg/kg BW across all 5 days of alcohol reaccess = ^†p < 0.001.