Effects of ethanol, barbital, and lorazepam on brain monoamines in rat lines selectively outbred for differential sensitivity to ethanol.

The acute effects of ethanol, barbital, and lorazepam on the synthesis and metabolism of brain monoamines were studied in the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) lines of rats, which have been selected for differential motor impairment after ethanol administration. The ethanol-sensitive ANT rats are also more sensitive than the ethanol-insensitive AT rats to the motor impairment caused by barbital and lorazepam. Ethanol increased, whereas barbital and lorazepam decreased, the synthesis of catecholamines in several regions of the brain. Ethanol did not affect the formation of DOPAC, whereas barbital and lorazepam reduced it. Similarly, the accumulation of 5-HTP was increased after administration of ethanol, but was decreased after administration of barbital or lorazepam. Ethanol, barbital and lorazepam decreased the formation of 5-HIAA. The rat lines did not differ in any of these responses. Some differences could, however, be demonstrated between the AT and ANT rats in the effects of the three drugs on the levels of the brain monoamines. Although the importance of these differences in the differential sensitivity to these drugs between the two lines is difficult to determine, the role of central monoaminergic mechanisms cannot be excluded. These findings also suggest that the motor impairment induced by ethanol, barbiturates, and benzodiazepines is probably not primarily based on the monoaminergic systems.