Central D-Ala2-Met5-enkephalinamide mu/delta-opioid receptor activation blocks behavioral sensitization to...

The present investigation revealed that intraventricular administration of the anxiogenic substance CCK-8S (50 ng) decreased responding for previously rewarding brain stimulation (intracranial self-stimulation; ICSS) and subsequently increased brain stimulation threshold determinations from the dorsal aspects of the ventral tegmental area (VTA) immediately following CCK administration. While central administration of the mixed mu/delta opioid receptor agonist D-Ala(2)-Met(5)-enkephalinamide (DALA; 1 microg) was ineffective in abrogating CCK induced ICSS deficits during the immediate post-stressor interval, DALA restored ICSS brain stimulation thresholds to basal values 24, 48 and 168 h following CCK challenge. At 18 days following the initial 50 ng CCK-8S and/or DALA challenges, mice were exposed to a previously determined non-anxiogenic dose of CCK-8S (5 ng). Among mice which received an intervening dose of saline following the 50 ng CCK-8S challenge, depressed ICSS responding and elevated brain stimulation thresholds were evident during the immediate (Day 18), 24- (Day 19) and 48-h (Day 20) test sessions relative to mice that received an intervening dose of DALA on Day 1. These data imply that while CCK induces relatively protracted and exaggerated behavioral disturbances, mu/delta opioid-receptor activation may block CCK-induced behavioral sensitization and change the course of psychopathology.