Effects of drugs on blood-brain barrier permeability in rats chronically intoxicated by ethanol

Male Wistar rats were divided in free choice conditions into heavy-drinkers consuming greater than 3.5 g/kg of ethanol daily (HD), and light-drinkers consuming less than 2.0 g/kg/day (LD). Subsequent 30 day intragastric administration of 25% ethanol (8-11 g/kg/day) caused an increase in permeability of the BBB to 14C-tyrosine, 14C-tryptophan and 14C-DOPA at all the stages of alcoholization. At late stages of intoxication (20-30 days) the penetration of horseradish peroxidase (HRP) indicating pinocytosis was present. All the changes were more pronounced in LD than in HD rats. Disulfiram, and to a lesser extent phenazepam and diazepam, when repeatedly injected (for 16-30 days) together with ethanol aggravated its effects. Clonidine and haloperidol antagonized ethanol-induced increase of the BBB permeability to labelled compounds and HRP in the two groups of rats. Picamilon, lithium oxybutyrate, chlorpromazine and alpha-tocopherol had little effect on the penetration of radioactive tracers but effectively antagonized the penetration of HRP. The other drugs were without effects on the BBB regulatory and barrier functions altered by chronic alcoholization. In view of the BBB dysfunction in chronic alcoholics the adequacy of the above-mentioned drugs for their treatment is discussed.