What is learned during opiate withdrawal conditioning? Evidence for a cue avoidance model

Abstract

How conditioned opiate withdrawal gives rise to avoidance behaviour was examined using a defensive burying procedure in rats made dependent with a morphine pellet. The subjects underwent withdrawal precipitated by naloxone (0.1 mg/kg, SC) on two or three occasions in a box containing only a small object. When exposed to the object in the presence of sawdust one or more days later, the subjects avoided contact and buried this object, i.e., pushed and piled the sawdust against it. The behaviour was seen only when withdrawal had been paired with the object, which was the case even with a choice of objects on the test. Approach but no burying was seen in nondependent animals when the object was paired with 1 mg/kg morphine. Burying, therefore, was concluded to be a defensive response elicited in rats by an object specifically paired with precipitated opiate withdrawal. Consideration of burying and other defensive responses reported to be elicited by cues of withdrawal (conditioned place and taste aversion, and suppression), with respect to the behavioural demands of these responses and the test conditions needed to see them, suggested that a goal of avoidance may be a primary event encoded in a withdrawal cue, as is known for predictors of nonpharmacological noxious events (e.g., shock).