Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat.
Carnosine (beta-alanyl-l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4-5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.
Wu
Xiao-hua
XH
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Ding
Mei-ping
MP
Zhu-Ge
Zheng-Bing
ZB
Zhu
Yuan-Yuan
YY
Jin
Chun-lei
CL
Chen
Zhong
Z
D000818:Animals; D002336:Carnosine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists; D006632:Histamine / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D018756:GABA Antagonists; D006632:Histamine; D002336:Carnosine; D010433:Pentylenetetrazole