Gender difference in epileptogenic effects of 2-BFI and BU224 in mice.
Imidazoline I2 receptors are involved in pain modulation and psychiatric disorders and its ligands may represent a new therapeutic strategy against pain and depression. In particular, 2-BFI and BU224 are the two most widely studied I2 receptor ligands and have antinociceptive and antidepressant-like activities in rodents. However, little is known of the toxicological effects and potential gender differences of these I2 receptor ligands. This study examined the epileptogenic activities of 2-BFI and BU224 in male and female mice and also examined their underlying receptor mechanisms. 2-BFI (10-40 mg/kg, i.p.) and BU224 (10-40 mg/kg) produced epileptic seizures in a dose-related manner, as did the epileptogenic agent, pentylenetetrazole (PTZ, 15-60 mg/kg). However, female mice were significantly more sensitive than male mice in all the measures. The commonly used I2 receptor antagonist, idazoxan (10mg/kg), did not block the onset and magnitude of the epileptic seizures or lethality induced by 2-BFI and BU224. When studied in combination, PTZ potentiated the epileptogenic effect of 2-BFI and BU224. The lack of antagonism by idazoxan of the epileptogenic activities of 2-BFI and BU224 suggests that the epileptogenic effects of 2-BFI and BU224 are mediated by non-imidazoline I2 receptors and that I2 receptors remain a viable therapeutic target for neurological disorders such as pain.
Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Road, Wuhan, Hubei 430071, PR China.
Jia-Wei
JW
Min
Bi-Wen
BW
Peng
Xiaohua
X
He
Yanan
Y
Zhang
Jun-Xu
JX
Li
D000818:Animals; D001572:Benzofurans / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000009:adverse effects* / Q000378:metabolism; D054755:Imidazoline Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*; D012727:Sex Characteristics
C105826:BU 224; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; C487767:imidazoline receptor 2; C103723:2-(2-benzofuranyl)-2-imidazoline
2-BFI; BU224; Idazoxan; Imidazoline I(2) receptor; Mice; Seizure