[Involvement of endogenous histamine in modulatory effect of morphine on seizure susceptibility in mice]
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Updated: Jul 15, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Zheng-Bing Zhu-Ge1, Yuan-Yuan Zhu, Deng-Chang Wu
1Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310058, China.
Objective:
To investigate the modulatory effects of morphine on the susceptibility to pentylenetetrazole-induced seizures, and the involvement of endogenous histamine in this process.
Methods:
Both the wild-type (WT) mice and histidine decarboxylase (a key enzyme for histamine biosynthesis) deficient (HDC-KO) mice were subcutaneously injected with different doses of morphine, and 1 hour later the pentylenetetrazole solution (1.5 %) was infused into the tail vein at a constant rate of 0.3 ml/min. The minimal dose of pentylenetetrazole (mg/kg) needed to induce myoclonic jerks and clonus convulsion was recorded as the thresholds of seizures.
Result:
In WT mice, morphine dose-dependently decreased the thresholds of both myoclonic jerks and clonus convulsion. In HDC-KO mice, morphine at 10 mg/kg only significantly decreased the threshold of myoclonic jerks from (38.6 +/-2.9)mg/kg to (32.5 +/-0.7)mg/kg, but had no significant effect on the threshold of clonus convulsion [from (51.8 +/-2.1)mg/kg to (47.6 +/-1.2)mg/kg]. In addition, the value of decreased myoclonic jerks (15.8 +/-1.4)% and clonus convulsion (8.3 +/-0.9)% thresholds were much lower in HDC-KO mice than in WT mice [(26.1 +/-2.5)% and (20.8 +/-2.4)%, respectively].
Conclusion:
Morphine can decrease the thresholds of pentylenetetrazole in induction of seizure, and the endogenous histamine may be involved in this process.
