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.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology / Q000187:drug effects*; D012653:Self Stimulation / Q000187:drug effects*
D009270:Naloxone