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

Psychopharmacology (Berl). 2001 Mar 1;154(2):213-20. doi: 10.1007/s002130000650.


Rationale: Chronic unpredictable stress, in which the type and timing of stress exposures are varied, alters protein levels in the mesolimbic DA system in a manner previously shown to be associated with enhanced behavioral responsiveness to cocaine. Chronic exposure to the same or predictable stress (restraint) does not. Thus, we examined the effects of chronic unpredictable and chronic predictable (restraint) stress on the locomotor activating and place conditioning effects to low cocaine doses.

Objective: To test whether chronic unpredictable stress enhances the sensitivity to the behavioral effects of cocaine.

Methods: Rats were exposed to 10 days of chronic unpredictable stress, of chronic predictable (restraint) stress, or were not stressed. One day following cessation of stress exposure, locomotor activity to cocaine (0 or 7.5 mg/kg) was assessed for 4 consecutive days and corticosterone levels on the last day were determined. In other experiments, the effects of the chronic stress procedures on cocaine (0.5 and 7.5 mg/kg) place conditioning using an unbiased procedure were assessed.

Results: Chronic unpredictable, but not chronic predictable, stress transiently increased the locomotor activating effects of cocaine and this was correlated positively with corticosterone levels. Chronic unpredictable, but not chronic predictable, stress also enhanced the place conditioning effects of cocaine: increased place preference was seen with the low dose and a pronounced place aversion occurred with the high dose.

Conclusions: These data demonstrate that chronic unpredictable stress enhances the behavioral effects of cocaine, including its aversive effects, whereas chronic predictable stress (restraint) is without effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Corticosterone / blood*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Stress, Physiological / blood*


  • Dopamine Uptake Inhibitors
  • Cocaine
  • Corticosterone