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Predisposing effects of neonatal visceral pain on abuse-related effects of morphine in adult male Sprague Dawley rats

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Abstract

Rationale

Adverse early life experiences are risk factors for drug abuse and addiction. Changes in brain opioid systems have been demonstrated in response to neonatal visceral pain (NVP), but the impact of these changes on abuse-related effects of morphine are unknown. The NVP procedure used models chronic visceral hyperalgesia persisting across development.

Objectives

Intravenous self-administration, drug discrimination, and locomotor activity were used to compare the abuse-related effects of morphine in NVP and control rats.

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.

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Authors and Affiliations

  1. Interdisciplanary Biomedical Sciences Program, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Andrew P. Norwood

  2. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences College of Medicine, 4301 West Markham, Slot 638, Little Rock, AR, 72205, USA

    Andrew P. Norwood & William E. Fantegrossi

  3. Center for Pain Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Elie D. Al-Chaer

Authors
  1. Andrew P. Norwood
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  2. Elie D. Al-Chaer
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  3. William E. Fantegrossi
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Correspondence to William E. Fantegrossi.

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Norwood, A.P., Al-Chaer, E.D. & Fantegrossi, W.E. Predisposing effects of neonatal visceral pain on abuse-related effects of morphine in adult male Sprague Dawley rats. Psychopharmacology 231, 4281–4289 (2014). https://doi.org/10.1007/s00213-014-3574-6

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  • DOI: https://doi.org/10.1007/s00213-014-3574-6

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