Oral ethanol self-administration: a behavioral pharmacological approach to CNS control mechanisms

Using rats which are self-administering ethanol in an operant situation, we have tested a variety of agonists and antagonists in an attempt to determine the role various CNS neurotransmitters may play in ethanol drinking. The major emphasis of the work has been on the dopaminergic and the benzodiazepinergic systems. This paper reviews prior work and provides new data on additional agonists and antagonists. The data suggest a possible reciprocal interaction between dopamine and benzodiazepine brain systems. This hypothesis is based on the change in pattern of lever responding which results when various agonists, antagonists and inverse agonists related to these neurotransmitters are compared. That is, similar changes in response pattern are found for dopamine agonists and benzodiazepine inverse agonists. On the other hand, dopamine antagonists and benzodiazepine agonists are similar to each other and produce a different set of changes. A neural circuit for a reciprocal interaction between the ventral tegmentum and the nucleus accumbens is proposed as one possible pathway which may be involved in these observations.