Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

Stress enhances the locomotor stimulant and discriminative stimulus effects of several addictive drugs (e.g., morphine) in rodents, yet interactions between stress and nicotine's effects in these behavioral models have not been well established. To this end, the current studies examined the effects of restraint stress on nicotine-induced locomotor activity and nicotine discrimination in rats. We used a novel approach in which onset of stress and nicotine administration occurred concurrently (i.e., simultaneous exposure) to simulate effects of stress on ongoing tobacco use, as well as a more traditional approach in which a delay was imposed between stress and nicotine administration (i.e., sequential exposure). Simultaneous exposure to stress reduced the rate of locomotor sensitization induced by daily injections of nicotine (0.4 mg/kg, s.c.). A lower dose of nicotine (0.1 mg/kg, s.c.) produced modest effects on activity that were generally unaffected by simultaneous exposure to stress. Sequential exposure to stress and nicotine (0.4 mg/kg, s.c.) slightly suppressed nicotine-induced activity but did not influence rate of locomotor sensitization. Neither simultaneous nor sequential exposure to stress influenced the discriminative stimulus effects of nicotine (0.01-0.2 mg/kg, s.c.). These data show that restraint stress reduces nicotine's locomotor stimulant effects, particularly when onset of stress and nicotine exposure occurs simultaneously, but does not influence nicotine discrimination. These findings contrast with the ability of stress to enhance the effects of other drugs in these models. This study also suggests that studying the influence of simultaneous stress exposure on drug effects may be useful for understanding the role of stress in addiction.