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Published on: July 29, 2014
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
Abstract:
In the present study, the influence of withdrawal from repeated administration of morphine on intra-ventral hippocampal microinjection of histamine-induced anxiety-like behavior was investigated in male Wistar rats. Three days subcutaneous administration of morphine (5-10 mg/kg) followed by five days free of the drug decreased the percentage open arm time and the percentage open arm entries. Intra-ventral hippocampal administration of histamine (2.5-7.5 microg/rat) decreased percentage open arm time and percentage open arm entries. Intra-ventral hippocampal histamine-induced anxiogenic effect was reversed in animals that had previously received the three days morphine (7.5 mg/kg) followed by five days free of the drug. Intra-ventral hippocampal administration of pyrilamine (5-20 microg/rat) or ranitidine (10-40 microg/rat) decreased percentage open arm time and percentage open arm entries. Pyrilamine- or ranitidine-induced anxiogenic effect was not changed in animals that had previously received the three days morphine (7.5 mg/kg) followed by five days free of the drug. Intra-ventral hippocampal injections of clobenpropit increased percentage open arm time. The percentage open arm time and percentage open arm entries were decreased in the morphine-treated animals compared with non-morphine-treated controls. Percentage open arm entries and locomotor activity was reduced with some doses of clobenpropit. It can be concluded that the histamine system is involved in anxiety-like behavior, and repeated injections of morphine followed by five days free of the drugs interact with histamine receptor mechanism.
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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