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 transduction pathways will suppress the initiation of cocaine self-administration was examined in this investigation. To test this hypothesis, the effects of the administration of the cAMP-specific (type IV) phosphodiesterase inhibitors, rolipram and Ro 20-1724, on cocaine self-administration were determined. 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 of the first cocaine infusion and a reduction in the number of infusions obtained 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 administration. Responding after drug-induced delays tended to be at control levels. These results suggest that cAMP-specific phosphodiesterase inhibitors may inhibit the initiation of operant responding for either cocaine or food. However, the extent to which these actions involve specific effects on central motivational systems as opposed to other mechanisms remains to be determined.
Knapp
C M
CM
National Institute on Drug Abuse/Boston Veterans Affairs, Medication Development Research Unit, MA, USA.
Foye
M M
MM
Ciraulo
D A
DA
Kornetsky
C
C
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D020889:Rolipram; D012646:Self Administration