Ziva D Cooper1, Yong-Gong Shi, James H Woods. 1. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, Substance Use Research Center, 1051 Riverside Dr, New York, NY 10032, USA. zc2160@columbia.edu
Abstract
RATIONALE AND OBJECTIVE: Opioid withdrawal increases the reinforcing effectiveness of the μ-opioid agonist remifentanil in rodents. The current study explored the selectivity of this effect by assessing operant behavior maintained by drug and non-drug reinforcers, remifentanil, cocaine, a palatable liquid food, and standard food pellets, as a function of opioid dependence and withdrawal. MATERIALS AND METHODS: Operant responding exhibited by nondependent, morphine-naïve groups was compared with responding exhibited by morphine-dependent and withdrawn groups. Dependence was established using a noncontingent morphine dosing procedure that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state. Behavior maintained by remifentanil (0.10-10.0 μg/kg/infusion), cocaine (0.032-1.0 mg/kg/infusion), a palatable liquid food reinforcer (3.2-100.0% Vanilla Ensure® and water), or food pellets was assessed in dependent and nondependent groups. RESULTS: Morphine withdrawal enhanced remifentanil self-administration, resulting in an upward and rightward shift of the descending limb of the dose-response curve, and increased operant responding for both food reinforcers. However, opioid withdrawal did not affect cocaine self-administration, nor did it affect responding for water. CONCLUSIONS: Enhanced operant responding observed under opioid-dependent and withdrawn conditions, while selective, is generalized to some nonopioid reinforcers.
RATIONALE AND OBJECTIVE: Opioid withdrawal increases the reinforcing effectiveness of the μ-opioid agonist remifentanil in rodents. The current study explored the selectivity of this effect by assessing operant behavior maintained by drug and non-drug reinforcers, remifentanil, cocaine, a palatable liquid food, and standard food pellets, as a function of opioid dependence and withdrawal. MATERIALS AND METHODS: Operant responding exhibited by nondependent, morphine-naïve groups was compared with responding exhibited by morphine-dependent and withdrawn groups. Dependence was established using a noncontingent morphine dosing procedure that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state. Behavior maintained by remifentanil (0.10-10.0 μg/kg/infusion), cocaine (0.032-1.0 mg/kg/infusion), a palatable liquid food reinforcer (3.2-100.0% Vanilla Ensure® and water), or food pellets was assessed in dependent and nondependent groups. RESULTS:Morphine withdrawal enhanced remifentanil self-administration, resulting in an upward and rightward shift of the descending limb of the dose-response curve, and increased operant responding for both food reinforcers. However, opioid withdrawal did not affect cocaine self-administration, nor did it affect responding for water. CONCLUSIONS: Enhanced operant responding observed under opioid-dependent and withdrawn conditions, while selective, is generalized to some nonopioid reinforcers.