[Involvement of endogenous histamine in modulatory effect of morphine on seizure susceptibility in mice].
To investigate the modulatory effects of morphine on the susceptibility to pentylenetetrazole-induced seizures, and the involvement of endogenous histamine in this process.



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.



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].



Morphine can decrease the thresholds of pentylenetetrazole in induction of seizure, and the endogenous histamine may be involved in this process.
Zhu-Ge
Zheng-Bing
ZB
Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310058, China.
Zhu
Yuan-Yuan
YY
Wu
Deng-Chang
DC
Jin
Chun-Lei
CL
Chen
Zhong
Z
D000818:Animals; D004198:Disease Susceptibility / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009207:Myoclonus / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology; D010433:Pentylenetetrazole; D011897:Random Allocation; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000187:drug effects
D009294:Narcotics; D009020:Morphine; D006632:Histamine; D006640:Histidine Decarboxylase; D010433:Pentylenetetrazole