Prazosin acts centrally to reduce yohimbine-induced alcohol seeking. The Fos mapping study suggests candidate sites where it may act. Doxazosin is also effective in reducing yohimbine-induced reinstatement. These data provide information on the mechanisms of alpha-1 antagonists on yohimbine-induced alcohol seeking and indicate their further investigation for the treatment of alcoholism.

Dependence on drugs has enduring effects on drug intake and relapse. The role of choice in enhanced susceptibility to drug use in drug dependence has been little studied. Here we determine the effects of alcohol dependence on the choice between alcohol and a non-drug reward, saccharin, using the discrete choice model in food-restricted male rats. We trained rats to self-administer alcohol (12% w/v) and saccharin (0.05, 0.1%), tested their choice of alcohol vs. saccharin, and determined the effects of deprivation and intertrial interval (ITI) duration on choice. We then determined the effects of alcohol dependence, induced by repeated intermittent exposure to alcohol vapor on choice of alcohol vs. saccharin (0.1%) in discrete choice trials as well as on the effects of adulteration of alcohol with quinine on choice. We trained another group of rats to self-administer intravenous (i.v.) nicotine (0.03 mg/kg/infusion) and oral saccharin (0.1%), determined their choice, and examined the roles of ITI duration and concurrent access on choice. Rats chose equivalent amounts of 0.05% saccharin and 12% alcohol, showed a stronger choice for 0.1% saccharin, and alcohol and saccharin choice were modestly decreased and increased, respectively, by deprivation. Alcohol dependence led to profound increases in the choice of alcohol over saccharin while adulteration of alcohol with quinine did not affect choice in non-dependent or dependent rats. Rats showed marked choice for 0.1% saccharin over i.v. nicotine. The strong effect that dependence had on alcohol choice is an important validation of the discrete choice procedure.

Operant responding for IV nicotine may rapidly come under habitual control, potentially contributing to the tenacity of tobacco use.