Metronidazole influences the development of neural tolerance to ethanol

The duration of the loss of the righting reflex (LoRR) was measured in Swiss Webster (SW) and DBA/2 mice following intraperitoneal injection of ethanol or metronidazole alone or together. A single injection of ethanol induced to short LoRR in SW mice and a long LoRR in DBA/2 mice. Metronidazole did not induce LoRR in either strain. When the mice were exposed daily to ethanol for five days, the duration of the LoRR was prolonged in SW mice and shortened in DBA/2 mice. This indicates the development of increased neural sensitivity to ethanol in SW mice and of neural tolerance to ethanol in DBA/2 mice. The response in SW mice to administration of ethanol and metronidazole together did not differ from their response to ethanol alone. However, the duration of the LoRR in DBA/2 mice injected repeatedly with the two drugs was longer than that observed with ethanol alone. Thus metronidazole appears to inhibit the development of neural tolerance to ethanol in DBA/2 mice but has no effect on ethanol induced LoRR in SW mice.