Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats.
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.


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exhibited by nondependent, morphine-naïve groups was compared with responding exhibited by morphine-dependent and withdrawn groups.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that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state.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Enhanced operant responding observed under opioid-dependent and withdrawn conditions, while selective, is generalized to some nonopioid reinforcers.
Cooper
Ziva D
ZD
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
Shi
Yong-Gong
YG
Woods
James H
JH
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists; D012055:Reinforcement Schedule; D000077208:Remifentanil; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D000701:Analgesics, Opioid; D010880:Piperidines; D017450:Receptors, Opioid, mu; D009020:Morphine; D003042:Cocaine; D000077208:Remifentanil