Sex-specific control of flurothyl-induced tonic-clonic seizures by the substantia nigra pars reticulata during development.
Sex-specific control of flurothyl-induced tonic-clonic seizures by the substantia nigra pars reticulata during development.
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发育过程中黑质网状部对氟洛酯诱导的强直阵挛发作的性别特异性控制。
DOI：
10.1016/j.expneurol.2006.04.005
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发表时间：
2006
影响因子：
5.3
通讯作者：
Moshé,SolomonL
中科院分区：
文献类型：
--
作者：
Velísek,Libor;Velísková,Jana;Giorgi,FilippoS;Moshé,SolomonL
黑质网状部(SNR)在控制阵挛发作中发挥着重要的年龄和性别特异性作用。它对强直-阵挛发作的控制是相互矛盾的。我们研究了信噪比在氟乙胺诱发雄性、雌性和新生去势雄性大鼠强直-阵挛发作中的作用。在成年雌性大鼠中，阴道阻抗决定了孕酮/雌激素比率的变化。出生后不同日龄的大鼠在SNR前部或SNR后部注入蝇草酚或赋形剂。此外，在15日龄(P15)和成年雄性大鼠中，注入Zapa(GABA(A)受体激动剂)或AP7(NMDA受体拮抗剂)。强直-阵挛发作阈值在雌雄大鼠之间的发育曲线不同，可能是由于雄性大鼠出生后早期睾酮激增所致。另一方面，改变成年雌性大鼠的雌/孕激素比值对惊厥阈值没有影响。黑质内苍蝇酚仅对幼年大鼠强直-阵挛发作有促惊厥作用，且这种作用依赖于围产期睾酮水平的升高。ZAPA对P15大鼠有抗惊厥作用，但对成年大鼠不起作用。只有AP7在成年大鼠和P15大鼠中都有抗惊厥作用。结果表明，氟乙基诱发强直-阵挛发作阈值的形成受生后睾酮的控制。虽然SNR中的GABA能抑制影响发育中大鼠的强直-阵挛发作，但只有NMDA拮抗剂在整个发育过程中具有一致的抗惊厥作用。
The substantia nigra pars reticulata (SNR) plays an important age- and sex-specific role in control of clonic seizures. Its involvement in control of tonic–clonic seizures is contradictory. We investigated the role of the SNR in the tonic–clonic seizures induced in male, female and neonatally castrated male rats using flurothyl. In adult female rats, vaginal impedance determined the changes in progesterone/estrogen ratio. Rats at various postnatal ages received infusions of muscimol or vehicle in the SNRanterior or SNRposterior. Furthermore, in 15-day-old (P15) and adult male rats, ZAPA (a GABA(A) receptor agonist) or AP7 (an NMDA receptor antagonist) was infused. The developmental profile of tonic–clonic seizure threshold differed between male and female rats possibly due to early postnatal testosterone surge in male rats. On the other hand, changing estrogen/progesterone ratio in cycling adult female rats had no effect on seizure threshold. Intranigral muscimol had proconvulsant effects on tonic–clonic seizures only in immature rats, and this effect was dependent on the perinatal testosterone surge. ZAPA had anticonvulsant effects in P15 rats but was not effective in adult rats. Only AP7 had anticonvulsant effects in both adult and P15 rats. Results indicate that thresholds for flurothyl-induced tonic–clonic seizures develop under the control of postnatal testosterone. Although GABAergic inhibition in the SNR affects tonic–clonic seizures in developing rats, only the NMDA antagonist had consistent anticonvulsant effects throughout development.