The results of this study demonstrate that selectively bred alcohol-preferring P rats, compared with Sprague–Dawley rats, are less sensitive to the aversive effects of alcohol. Sprague–Dawley rats showed a long-lasting decrease in alcohol consumption and preference for 4 weeks after a single alcohol pretreatment. On the other hand, the P rats given the same alcohol pretreatment showed no such effect. Without alcohol pretreatment, there were no discernible differences between Sprague–Dawley and P rats in either the amount of alcohol consumed and the percent alcohol preference. The lack of difference in alcohol preference between Sprague–Dawley and P rats before being treated with alcohol is likely contributed to the palatability of 5% (v/v) alcohol. It is likely that at higher concentrations of alcohol, the P rats will drink significantly more alcohol than Sprague–Dawley rats. The increased alcohol consumption seen in P rats seems to be entirely due to a lack of the normal aversion to initial alcohol treatment rather than increased preference. It has previously been shown that the P rats self-administer significant quantities of alcohol intragastrically, indicating that post-absorptive effects of alcohol, rather than its taste or smell, are reinforcing for the P rats (Waller et al., 1983a
). It has also been demonstrated that P rats find the post-ingestional effects of high dose of alcohol less aversive and low dose of alcohol more rewarding than their control counterpart, the NP rats (Froehlich et al., 1988
). The possible effects of taste in the current experiment should be ruled out because alcohol solution was delivered directly into the stomach and not into the mouth. Genetic differences in sensitization and tolerance development to alcohol between the P and NP rats have also been reported. Kurtz and colleagues (1996
) studied the initial sensitivity to alcohol and the development of tolerance comparing the P with the NP rats. They demonstrated that P rats were less sensitive to the behaviorally impairing effects of alcohol than were NP rats, as evidenced by longer latency to lose righting reflex and a shorter time to recover following an acute dose of alcohol. It has also been shown that within-session tolerance to alcohol is developed in P rats (Waller et al., 1983b
). Thus, it can be speculated that the combination of lack or less sensitivity to alcohol, less aversion to alcohol and development of acute tolerance to alcohol may serve to increase alcohol intake in P rats. As mentioned in the Introduction
, in the conditioned taste aversion (CTA) paradigm (Froehlich et al., 1988
) and in the conditioned place preference (CPP) paradigm (Stewart et al., 1996
), both P and NP rats showed aversion to alcohol. However, the magnitude of aversion to alcohol was significantly less in P rats compared with NP rats. In one study, no difference was found between P and NP rats using the CPP paradigm (Schechter, 1992
). Our results should not be directly compared with CTA and CPP results because measuring drinking alcohol is the most appropriate test for testing aversion to alcohol in rats that have been selectively bred to drink alcohol.
The fact that one single intragastric administration of alcohol impaired acquisition of alcohol drinking in Sprague–Dawley rats but not in P rats suggests that this selectively bred line might have less aversion to alcohol than the outbred Sprague–Dawley line. One can speculate that the diminished aversion to alcohol may partly explain the high level of drinking in selectively bred P rats.
Interestingly, similar findings have been reported in humans regarding the importance of diminished aversive effects of alcohol in alcoholics. A lower level of response, i.e. lower sensitivity to subjective and intoxicating effects of alcohol, has been repeatedly demonstrated in adult children of alcoholics (Schuckit and Smith, 1996
; Schuckit and Gold, 1998
; Schuckit and Smith, 2000
; Schuckit et al., 2005, 2006, 2009
; Trim et al., 2009
). Indeed, low level of response to alcohol is shown to be a unique risk factor for future heavy drinking (Trim et al., 2009
). Clearly, genetic factors play a major role in lower sensitivity to alcohol, which may lead to heavy drinking.
The current results clearly call for further research, especially regarding the relative roles of pharmacokinetic and pharmacodynamic effects underlying the diminished aversive effects of alcohol in P rats. However, since P rats and its control counterpart, NP rats, metabolize alcohol at the same rate (Waller et al., 1983b
), it is unlikely that the lack of aversion to alcohol in P rats is of pharmacokinetic nature. Determining critical pharmacodynamic factors underlying this effect will be key not only for understanding the basic biology of addiction but also for developing new treatments to combat alcoholism. This study demonstrates the importance of aversion to initial alcohol exposure in the control of later voluntary consumption. The lack of normal aversion can be a key factor leading to heavy alcohol consumption and increased risk for alcoholism.