The 'direct' pharmacological effects of heroin on operant responding and activity: the yoked-operant procedure.

The present study demonstrates a method which enables separation of the 'direct' pharmacological effects of heroin on activity and operant responding from the 'indirect' reinforcing effects of heroin. Experiment I was carried out at 0.1 mg/kg heroin with naive male albino Wistar rats (N = 21) from a La Trobe University (Bundoora, Australia) colony. Experiments II and III were carried out at 0.05 mg/kg (N = 21) and 0.2 mg/kg (N = 21) heroin doses with Wistar rats from a Monash University (Clayton, Australia) colony. Each experiment consisted of a 5-day pre-training period and a 10-day experimental period. Food-contingent operant behaviour was shaped in 14 animals during the first 4 days of the pre-training period. On day 5, baseline data was taken. Pairs of animals were then randomly yoked to one of seven naive 'executive' animals and the executive animals were allowed to self-inject heroin. Each self-injection of heroin by an executive animal led to a simultaneous injection of heroin to a yoked-heroin animal, and a simultaneous injection of saline to a yoked-saline animal. Results of 1-h data showed a significant decrement in food-contingent operant behaviour only for the yoked-heroin animals in the 0.2 mg/kg and 0.05 mg/kg groups. A significant decrement in both food-contingent operant behaviour and activity was found for the yoked-heroin animals at all three doses studied when data from the first half of 1-h sessions only was examined. It was concluded that the rate of self-injection demonstrated by executive animals was limited by the direct pharmacological effects of heroin on activity, and that the impairment of responding for food reflected this direct pharmacological effect of heroin. A theoretical model of reinforcement strength was subsequently proposed.