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We have previously reported that UChA rats (genetically low ethanol consumer) develop tolerance to narcosis time easier than UChB rats (genetically high ethanol consumer). We also have reported that UChA rats develop tolerance to the hypothermic effect of ethanol, while in UChB rats the repeated administration of ethanol induces sensitization towards this effect. In the present paper the effects of alpha-methyl-p-tyrosine (AMPT)--a competitive inhibitor of norepinephrine synthesis--on ethanol-induced narcosis and hypothermia, as well as in the development of tolerance to these effects, were studied in both strains of rats. Results obtained show that AMPT pretreatment induced a significantly higher increase in narcosis time and hypothermia, as well as, greater susceptibility to ethanol toxicity in UChB than UChA rats. Furthermore, the simultaneous treatment with AMPT and ethanol did not change the development of tolerance to narcosis time in both strains and to hypothermia and sensitization in UChA and UChB rats respectively.

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.