The type IV phosphodiesterase inhibitors, Ro 20-1724 and rolipram, block the initiation of cocaine self-administration

The hypothesis that the selective activation of cyclic AMP (cAMP) signal tr ansduction pathways will suppress the initiation of cocaine self-administra tion was examined in this investigation. To test this hypothesis, the effec ts of the administration of the cAMP-specific (type IV) phosphodiesterase i nhibitors, rolipram and Ro 20-1724, on cocaine self-administration were det ermined. The effects of Ro 20-1724 treatment on operant responding for food also were examined. Both cocaine and food were delivered following a fixed -ratio 5 schedule. A significant increase in the latency for the delivery o f the first cocaine infusion and a reduction in the number of infusions obt ained per session were produced by treatment with either rolipram or Ro 20- 1724. Similar effects on responding for food were seen with Ro 20-1724 admi nistration. Responding after drug-induced delays tended to be at control le vels. These results suggest that cAMP-specific phosphodiesterase inhibitors may inhibit the initiation of operant responding for either cocaine or foo d. However, the extent to which these actions involve specific effects on c entral motivational systems as opposed to other mechanisms remains to be de termined. (C) 1998 Elsevier Science Inc.