Hyperbaric Oxygen Attenuates Withdrawal Symptoms by Regulating Monoaminergic Neurotransmitters and NO Signaling Pathway at Nucleus Accumbens in Morphine-Dependent Rats

Neurochem Res. 2018 Mar;43(3):531-539. doi: 10.1007/s11064-017-2447-x. Epub 2018 Jan 8.


In this study, we examined whether hyperbaric oxygen (HBO2) plays a detoxification role in withdrawal symptoms in a morphine-dependent rat model. The model was established through injections of morphine at increasing doses for 7 days. Withdrawal symptoms were induced by naloxone injection on the 8th day. The detoxification effect of HBO2 was evaluated using the withdrawal symptom scores, biochemical indices and neurotransmitters. Compared with the model group, HBO2 therapy significantly attenuated the withdrawal symptom scores, body weight loss and the level of norepinephrine level, whereas it increased the dopamine level and tyrosine hydroxylase expression in the nucleus accumbens. Moreover, HBO2 therapy substantially alleviated the NO, NOS, cAMP, and cGMP levels. Our findings indicate that HBO2 can effectively alleviate withdrawal symptoms induced by morphine dependence, and these effects may be attributed to the modulation of monoaminergic neurotransmitters and the suppression of the NO-cGMP signaling pathway.

Keywords: Hyperbaric oxygen; Morphine dependence; NO–cGMP signaling pathway; Neurotransmitters; Withdrawal symptoms.

MeSH terms

  • Animals
  • Hyperbaric Oxygenation*
  • Male
  • Morphine / pharmacology*
  • Morphine Dependence / metabolism
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neurotransmitter Agents / metabolism*
  • Nitric Oxide / metabolism*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Substance Withdrawal Syndrome / drug therapy


  • Narcotic Antagonists
  • Neurotransmitter Agents
  • Nitric Oxide
  • Naloxone
  • Morphine