Co-administration of nalbuphine attenuates the morphine-induced anxiety and dopaminergic alterations in

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Rahul Raghav1, Raka Jain2, Tony G Jacob3

  • 1National Drug Dependence Treatment Center, Department of Psychiatry, All India Institute of Medical Sciences, Room no. 4090, Teaching Block, New Delhi, 110029, India.

Psychopharmacology
|March 3, 2021
PubMed
Abstract

Insights

Chronic nalbuphine administration, unlike acute, effectively reduces morphine-induced anxiety and dopaminergic system changes in rats. This suggests nalbuphine

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Opioid dependence, particularly from morphine, is linked to μ-opioid receptor activation and subsequent anxiety-like behaviors.
  • Chronic morphine use alters the mesolimbic dopaminergic system, contributing to behavioral and functional changes.
  • Nalbuphine, a mixed μ/κ-opioid agonist, exhibits distinct effects compared to morphine, but its potential to counteract morphine-induced issues is not fully understood.

Purpose of the Study:

  • To investigate and compare the acute versus chronic effects of nalbuphine on morphine-induced anxiety.
  • To evaluate nalbuphine's impact on dopaminergic alterations associated with morphine dependence.
  • To assess nalbuphine's potential in mitigating side effects of chronic morphine use.

Main Methods:

  • Rats were rendered opioid-dependent using escalating doses of morphine.
  • Anxiety-like behaviors were assessed using an Activity Monitor.
  • Brain tissue analysis included measuring cyclic adenosine monophosphate (cAMP) levels and tyrosine hydroxylase (TH) expression (transcriptional and translational) following acute and chronic co-administration of nalbuphine with morphine.

Main Results:

  • Morphine dependence significantly increased anxiety, cAMP levels, and decreased TH expression.
  • Chronic co-administration of nalbuphine successfully attenuated morphine-induced anxiety and elevated cAMP levels.
  • Chronic nalbuphine treatment also upregulated TH expression, while acute treatment showed no such mitigating effects.

Conclusions:

  • Chronic administration of nalbuphine demonstrates efficacy in counteracting anxiety and dopaminergic pathway alterations induced by morphine.
  • Nalbuphine shows potential as a therapeutic agent for managing opioid addiction and its associated behavioral and neurochemical consequences.
  • The timing of nalbuphine administration (chronic vs. acute) is critical for its therapeutic effects in mitigating morphine's adverse impacts.
Keywords:
AnxietyCo-administrationDopamineMorphineNalbuphineNaloxone

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