Effects of acamprosate on ethanol-seeking and self-administration in the rat

Background: Acamprosate (calcium acetyl homotaurinate) has been used clinic ally to treat relapse in alcoholics. In rats, it has been shown to decrease ethanol, but not water, self-administration after ethanol deprivation. Methods: To further investigate the effect of acamprosate on reinforced beh aviors in rats, the present experiment used: (1) bath ethanol and sucrose r einforcer solutions to better assess the distinct effects of acamprosate on ethanol-directed behaviors, and (2) an operant model that procedurally sep arates the "cost" to begin drinking from consuming the reinforcer solutions to dissociate the effects of acamprosate on appetitive versus consummatory processes. In daily sessions (5 days/week), rats (n = 6/group) were traine d to make 30 lever-press responses to gain access for 20 min to a sipper tu be containing either ethanol (10%,) or sucrose (3%). After stable respondin g, acamprosate treatment was given. Three doses were tested (50, 100, and 2 00 mg/kg/injection, intraperitoneally), one dose per week. Each week, a tot al of four injections were given (21 and 2 hr before the operant sessions o ver 2 consecutive days). Results: At these doses, acamprosate had no effect on the measures of appet itive responding for either solution. However, all doses reliably decreased ethanol consumption on the 2nd day of treatment (from an average of 0.83 t o 0.63 g/kg). Analysis of the pattern of ethanol consumption showed that th e effects of acamprosate occurred after the onset of a normal pattern of in take, as measured by lick rate and size of the initial bout of drinking, wh ich suggested that acamprosate is most effective when combined with the pha rmacological effects of ethanol. Sucrose intake was unaffected by all acamp rosate treatments, which indicated that the treatment effects were specific to ethanol and not due to a general decrease in consummatory behavior. Conclusions: Overall, these results suggest that acamprosate is effective a t reducing total ethanol intake; but may not reliably alter subjects propen sity to begin a drinking bout as measured by this model. However, whether t his applies to the clinical use of acamprosate, where other types of reinfo rcement may also precipitate relapse drinking, is not certain.