Morphine blocks and naloxone enhances suppression of operant behavior by low doses of 3-isobutyl-1-methylxanthine.

Methylxanthines administered in high doses or in combination with the opiate antagonist naloxone produce symptoms resembling opiate withdrawal. Administration of isobutyl-1-methylxanthine (IBMX, 1.25-5.00 mg/kg) to rats which were performing a fixed-ratio 30 operant for food reinforcement caused a dose-dependent suppression of responding and a decrease in colonic temperature. Administration of behaviorally inactive doses of the opiate antagonist naloxone (1.25-5.00 mg/kg) 10 min after the beginning of the fixed-ratio 30 session significantly increased the behavioral effects of IBMX (1.25-5.00 mg/kg) injected 30 min before the session, with no consistent effect upon IBMX-induced hypothermia. The coadministration of behaviorally inactive doses of morphine (0.05-1.50 mg/kg) with IBMX (5.00 mg/kg) 30 min before the fixed-ratio 30 session antagonized the operant behavioral effects of IBMX. These results suggest that the operant behavioral effects of IBMX provide a model with which to examine the expression of opiate withdrawal without the confounding changes associated with the acute pharmacological actions of opiates.