Increasing the work requirements lowers the threshold of naloxone for reducing self-stimulation in the midbrain of rats.

Rats were trained to lever-press for intracranial self-stimulation (ICSS) with electrodes in the midbrain central gray area. The effects of naloxone (0.1-30.0 mg/kg, SC) on a continuous reinforcement (CRF) schedule were determined. Rats were then re-trained on higher fixed-ratio (FR) schedules, and naloxone was re-tested at FR: 5, 10, 15 and 20. Only moderate reductions in lever-pressing rates were obtained at the highest dose of naloxone under CRF and FR: 5 schedules. In contrast, pronounced, dose-dependent reductions in ICSS rates occurred at FR: 10, 15 and 20. The time-course for this reduction at FR: 20 was consistent with an opiate-antagonistic action of naloxone. The modest decrease in locomotor activity produced by naloxone in a matched group of control rats was not sufficient to account for the effects on ICSS. The threshold of naloxone for reducing the rate of ICSS lever-pressing was lowered by increasing the effort and/or time requirement for each reinforcement.