The attenuation of morphine-conditioned place preference following chronic mild stress is reversed by a CCKB receptor antagonist.

Chronic exposure to mild unpredictable stress has been found to abolish the acquisition of preference for a distinctive environment paired with morphine, whereas morphine induced conditioning place preference in non-stressed rats. Chronic treatment for 21 days with the tricyclic antidepressant imipramine reversed the motivational effects produced by chronic mild stress, and animals showed a place preference for the morphine-paired compartment. When the CCKB receptor antagonist PD-134,308 was co-administered with morphine in stressed animals during the conditioning period, the preference for the morphine-paired compartment was also re-established. The CCKB receptor antagonist given alone did not induce rewarding effects in this paradigm. These findings indicate that the administration of a CCKB receptor antagonist reversed the effects of chronic mild stress on opiate rewarding properties.