Withdrawal from repeated administration of morphine alters histamine-induced anxiogenic effects produced by

Mohammad-Reza Zarrindast1, Parvin Khodarahmi, Ameneh Rezayof

  • 1Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir

Insights

Morphine withdrawal in rats alters histamine-induced anxiety behaviors. Histamine in the hippocampus plays a role in anxiety, and morphine withdrawal affects this system.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Repeated morphine administration can lead to withdrawal symptoms.
  • The ventral hippocampus is implicated in anxiety-related behaviors.
  • Histamine neurotransmission is involved in regulating mood and anxiety.

Purpose of the Study:

  • To investigate the effect of morphine withdrawal on histamine-induced anxiety-like behavior in the rat ventral hippocampus.
  • To explore the role of histamine receptors in morphine withdrawal-associated anxiety.

Main Methods:

  • Male Wistar rats received subcutaneous morphine injections followed by a withdrawal period.
  • Anxiety-like behavior was assessed using the elevated plus maze, measuring percentage open arm time and entries.
  • Intra-ventral hippocampal microinjections of histamine, pyrilamine, ranitidine, and clobenpropit were administered.

Main Results:

  • Morphine withdrawal decreased anxiety-like behaviors.
  • Histamine administration into the ventral hippocampus induced anxiety-like behavior, which was reversed by prior morphine withdrawal.
  • Histamine receptor antagonists (pyrilamine, ranitidine) also induced anxiety-like behavior, unaffected by morphine withdrawal.
  • A histamine H3 receptor agonist (clobenpropit) increased open arm time, but reduced locomotor activity.

Conclusions:

  • The histamine system in the ventral hippocampus is involved in anxiety-like behavior.
  • Repeated morphine administration followed by withdrawal interacts with histamine receptor mechanisms.
  • These findings suggest a complex interplay between opioid withdrawal and the histaminergic system in modulating anxiety.

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