Chronic unpredictable stress, but not chronic predictable stress, enhancesthe sensitivity to the behavioral effects of cocaine in rats

Rationale: Chronic unpredictable stress, in which the type and timing of st ress exposures are varied, alters protein levels in the mesolimbic DA syste m in a manner previously shown to be associated with enhanced behavioral re sponsiveness to cocaine. Chronic exposure to the same or predictable stress (restraint) does not. Thus, we examined the effects of chronic unpredictab le and chronic predictable (restraint) stress on the locomotor activating a nd place conditioning effects to low cocaine doses. Objective: To test whet her chronic unpredictable stress enhances the sensitivity to the behavioral effects of cocaine. Methods: Rats were exposed to 10 days of chronic unpre dictable stress, of chronic predictable (restraint) stress, or were not str essed. One day following cessation of stress exposure, locomotor activity t o cocaine (0 or 7.5 mg/kg) was assessed for 4 consecutive days and corticos terone levels on the last day were determined. In other experiments, the ef fects of the chronic stress procedures on cocaine (0, 5 and 7.5 mg/kg) plac e conditioning using an unbiased procedure were assessed. Results: Chronic unpredictable, but not chronic predictable, stress transiently increased th e locomotor activating effects of cocaine and this was correlated positivel y with corticosterone levels. Chronic unpredictable, but not chronic predic table, stress also enhanced the place conditioning effects of cocaine: incr eased place preference was seen with the low dose and a pronounced place av ersion occurred with the high dose. Conclusions: These data demonstrate tha t chronic unpredictable stress enhances the behavioral effects of cocaine, including its aversive effects, whereas chronic predictable stress (restrai nt) is without effect.