Blockade of dopamine D1 receptors in male rats disrupts morphine reward in pain naïve but not in chronic pain states

J Neurosci Res. 2022 Jan;100(1):297-308. doi: 10.1002/jnr.24553. Epub 2019 Nov 12.

Abstract

The rewarding effect of opiates is mediated through dissociable neural systems in drug naïve and drug-dependent states. Neuroadaptations associated with chronic drug use are similar to those produced by chronic pain, suggesting that opiate reward could also involve distinct mechanisms in chronic pain and pain-naïve states. We tested this hypothesis by examining the effect of dopamine (DA) antagonism on morphine reward in a rat model of neuropathic pain.Neuropathic pain was induced in male Sprague-Dawley rats through chronic constriction (CCI) of the sciatic nerve; reward was assessed in the conditioned place preference (CPP) paradigm in separate groups at early (4-8 days post-surgery) and late (11-15 days post-surgery) phases of neuropathic pain. Minimal effective doses of morphine that produced a CPP in early and late phases of neuropathic pain were 6 mg/kg and 2 mg/kg respectively. The DA D1 receptor antagonist, SCH23390, blocked a morphine CPP in sham, but not CCI, rats at a higher dose (0.5 mg/kg), but had no effect at a lower dose (0.1 mg/kg). The DA D2 receptor antagonist, eticlopride (0.1 and 0.5 mg/kg), had no effect on a morphine CPP in sham or CCI rats, either in early or late phases of neuropathic pain. In the CPP paradigm, morphine reward involves DA D1 mechanisms in pain-naïve but not chronic pain states. This could reflect increased sensitivity to drug effects in pain versus no pain conditions and/or differential mediation of opiate reward in these two states.

Keywords: addiction; analgesia; antinociception; aversion; chronic pain; dependence; opioid; reward.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Pain* / drug therapy
  • Male
  • Morphine* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1
  • Reward

Substances

  • Receptors, Dopamine D1
  • Morphine

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