[Effects of amygdala kindled seizures on memory retention of passive-avoidance test in rats].

OBJECTIVE: To investigate the effects of amygdala kindled seizures on memory retention of passive-avoidance test in rats. METHODS: Chronic kindled seizures were achieved by daily application of electric stimulations on amygdala until the occurrence of 3 consecutive convulsive seizures. Then a passive-avoidance test was performed to measure memory retention ability in rats; another group of rats received an electric stimulation on amygdala 5 min before the training trail to observe the effects of acute seizure attack on memory retention ability. RESULT: In the training trail and the 1st day of the test trail, there was no difference in the latency to enter dark compartment between chronic kindled seizure group and its corresponding control group. However, the latency significantly increased at the 5 th day of test trail. In addition, the latency of acute seizure attack group rats significantly decreased at the 1 st day and 5 th day of test trail. CONCLUSION: Chronic amygdala kindled seizures increase memory retention of passive-avoidance test in rats, and acute seizure attack impairs this action.

Low-frequency stimulation of the tuberomammillary nucleus facilitates electrical amygdaloid-kindling acquisition in Sprague-Dawley rats.

Histamine plays a suppressive role in seizure. The tuberomammillary nucleus (TM) is the only locus of histaminergic neurons in the brain. To determine whether deep brain stimulation (DBS) of the TM provides protection against seizures, we tested the effects of low-frequency stimulation (LFS, 1 Hz), high frequency stimulation (HFS, 100 Hz), and electrolytic lesions of the TM on seizures generated by amygdaloid kindling, pentylenetetrazol (PTZ) and maximal electroshock (MES) in rats. LFS of TM accelerated the progression of behavioral seizure stage and increased the mean afterdischarge duration (ADD) during acquisition of amygdaloid-kindling seizures, but had no considerable anticonvulsive effect in fully kindled animals. It augmented the MES-induced seizures as well, but had no appreciable effects on PTZ-kindled seizures. In addition, both HFS and bilateral lesions of the TM exacerbated the progression of amygdaloid-kindling seizures. These results suggest that specific negative sites for DBS exist in the brain, such as the TM. This study indicates that it is crucial to choose a suitable target for DBS in the clinical treatment of epilepsy.

[Involvement of endogenous histamine in modulatory effect of morphine on seizure susceptibility in mice].

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.

[Injection of saline into unilateral central piriform cortex inhibits amygdaloid-kindled seizures in rats].

OBJECTIVE: To investigate the effect of microinjection of saline into unilateral central piriform cortex (cPC) on the generalized seizures in amygdaloid-kindled rats. METHODS: Different volumes of saline were injected into the right or left cPC of amygdaloid-kindled rats, and its effect on generalized seizures was observed. RESULT: Saline injection at different volumes 0.1 microl, 0.25 microl and 1 microl) significantly decreased the incidence and duration of generalized seizures (P<0.05), the anticonvulsant effect lasted for up to 10 d. In addition, 10 min after ipsilateral injection of saline the generalized seizure thresholds were significantly increased; while this effect was observed 30 min later when contralateral injection was used. CONCLUSION: Unilateral saline injection into cPC has a significant anticonvulsant effect, which might be used for treatment of human temporal lobe epilepsy in the future.

Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice.

In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that alpha-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine-histidine-histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.

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.