Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin.

The formation of tolerance to the hypothermic effect of ethanol was inhibited in rats after intraperitoneal injection of the neurotoxin DSP-4 50 mg/kg. The neurotoxin also significantly suppressed the ethanol withdrawal syndrome; hyperlocomotion, audiogenic seizures and spasticity. These behavioural changes were accompanied by a 52% decrease of the brain norepinephrine (NE) content, with no alterations in the dopamine or serotonin levels. The results indicate that intact NE neurons are necessary for the development of tolerance to ethanol-induced hypothermia and are involved in the expression of the ethanol withdrawal syndrome.