Behavioral Methodology Facilitating Ethanol Reward

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DESCRIPTION (provided by applicant): Although a rewarding component of ethanol (ETOH) use cannot be disputed, it is not a trivial task to isolate and test the positive reinforcing effects of ETOH in laboratory rats. For example, intravenous (IV) self-administration is a popular behavioral method for determining reward constituents of most abused drugs, but not ETOH. Indeed, there are few reports of IV ETOH self-administration and existing papers are limited in scope. In such studies, behavioral response requirements and ETOH intake levels are both extremely low, bringing into question whether the apparent motivational properties of IV ETOH are centrally mediated. Oral ETOH self-administration, however, is widely utilized and accepted as an index of rewarding ETOH effects. Unfortunately, even with the utilization of genetically selected rat lines, sustained exposure to oral ETOH is required before reliable intake is initiated, presumably to allow for habituation to the aversive ETOH taste. Yet, even when taste factors are circumvented (e.g., parenteral ETOH), prolonged exposure to ETOH is still required before EtOH-conditioned reward can be observed. After standard conditioning procedures, rats pre-exposed to ETOH demonstrate conditioned place preferences to EtOH-paired environments, but ETOH-naive rats show place aversions. These findings suggest the positive reinforcing effects of ETOH following ETOH pre-exposure may be due to EtOH-induced neuroadaptive alterations rather than orosensory habituation. This proposal describes a behavioral model formulated in our laboratory that ultimately resulted in high voluntary IV and oral ETOH intake. In pilot studies, rats pre-exposed to IV ETOH by self-administering IV EtOH/cocaine combinations, demonstrated reliable responding to IV ETOH alone. Self-administered IV EtOH intake (0.5-2.0 g/kg/lhr) corresponded with blood alcohol levels (BAL) of approx. 44-221 mg/dL. These BALs clearly indicate pharmacological effects of ETOH and (at the high end) have not previously been empirically demonstrated after voluntary ETOH intake. In addition, animals that self- administered IV ETOH alone subsequently drank approx. 0.65 g/kg of ETOH without oral ETOH sucrose-fading sessions. Further analyses of IV ETOH self-administration will allow identification of neurobiological substrates of the rewarding aspects of ETOH without interference from orosensory factors. This proposal will investigate parameters of ETOH intake and time course through behavioral analyses of IV and oral ETOH self-administration. In vivo microdialysis will also be used to compare EtOH-induced increases in accumbens dopamine levels between animals self-administering IV ETOH and those receiving ETOH via experimenter- administration.