Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward

Zhong Qiu Zhao, Yong Jing Gao, Yan Gang Sun, Cheng Shui Zhao, Robert W. Gereau IV, Zhou Feng Chen

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Opioids remain the most effective analgesics despite their potential adverse effects such as tolerance and addiction. Mechanisms underlying these opiate-mediated processes remain the subject of much debate. Here we describe opioid-induced behaviors of Lmx1b conditional knockout mice (Lmx1b f/f/p), which lack central serotonergic neurons, and we report that opioid analgesia is differentially dependent on the central serotonergic system. Analgesia induced by a κ opioid receptor agonist administered at the supraspinal level was abolished in Lmx1bf/f/p mice compared with their wild-type littermates. Furthermore, compared with their wild-type littermates Lmx1bf/f/p mice exhibited significantly reduced analgesic effects of μand σ opioid receptor agonists at both spinal and supraspinal sites. In contrast to the attenuation in opioid analgesia, Lmx1bf/f/p mice developed tolerance to morphine analgesia and displayed normal morphine reward behavior as measured by conditioned place preference. Our results provide genetic evidence supporting the view that the central serotonergic system is a key component of supraspinal pain modulatory circuitry mediating opioid analgesia. Furthermore, our data suggest that the mechanisms of morphine tolerance and morphine reward are independent of the central serotonergic system.

Original languageEnglish
Pages (from-to)14519-14524
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number36
DOIs
StatePublished - Sep 4 2007

Keywords

  • Behavior
  • Conditioned place preference
  • Mouse
  • Pain
  • Serotonin

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