Conditioning Factors in the Relationship between Stress and Opioid Self-Administration in Rats.

摘要

The present experiments examined the effect of stress on oral opioid (morphine and fentanyl ) self-administration (SA) and withdrawal, and further examined the role of conditioning factors in the relationship between stress and opioids in rats. In Experiment 1, male rats were exposed to four different conditions for each of the two drugs: Paired-stress groups were exposed to 15 min/day of immobilization (IM) stressor that reliably predicted the opioid SA period for 6 h/day in the home cage; Partial-Conditioning groups were exposed to 1M stressor that predicted the drug SA period in 50% of the days; Conditioned-Inhibition groups were exposed to IM stressor that predicted the absence of the drug; and Control groups were not exposed to the stressor. The Paired-stress and the Partial-Conditioning groups increased their drug SA and manifested a more severe withdrawal syndrome compared with the Conditioned Inhibition and Control groups. The experimental animals were further examined during a 30-day relapse phase conducted after 60 days of drug SA followed by 3 weeks of a drug-free, stress-free period. The original four experimental groups within each drug class were divided into two conditions. The stress groups were exposed to the IM stressor prior to the opioid SA period; and the Control groups were not exposed to the stressor. The stress groups increased their drug SA and manifested a more severe withdrawal syndrome compared with the Control groups. In Experiment. 2, rats were trained to lever press for fentanyl solutions in operant conditioning chambers. Rate of responding for the drug after exposure to electric footshock and without exposure to the stressor was the main measure in this experiment. Animals increased their fentanyl SA during the stress condition as compared to a non-stress condition.