Conclusions
NVP-induced changes in brain opioid systems have persistent pharmacological consequences into adulthood and may increase sensitivity to abuse-related effects of opioids across development.
Methods
Rats self-administered 0.3 mg/kg/inj morphine under an FR1 schedule, and dose-effect functions for morphine were then established. Separate rats were trained to discriminate 3.2 mg/kg morphine from saline under an FR20 schedule, and morphine dose-effect functions were then determined in the absence and presence of 0.1 mg/kg naltrexone. A third group of rats was tested with a range of morphine doses in an assay of locomotor activity, then injected daily with 10 mg/kg morphine to assess locomotor sensitization.
Results
NVP rats self-administered more morphine than controls at reinforcing doses. Discriminative stimulus effects of morphine were similar between groups, but in the presence of naltrexone, the ED50 for morphine was more than 12× greater in control rats than in NVP animals. Morphine did not stimulate locomotor activity at any tested dose in NVP rats, although significant effects were observed in controls. Finally, significant locomotor sensitization was observed only in NVP rats. Conclusions: NVP-induced changes in brain opioid systems have persistent pharmacological consequences into adulthood and may increase sensitivity to abuse-related effects of opioids across development.