cgp-62349 has been researched along with Seizures* in 2 studies
2 other study(ies) available for cgp-62349 and Seizures
Article | Year |
---|---|
GABAB receptors as a common target for hypothermia and spike and wave seizures: intersecting mechanisms of thermoregulation and absence epilepsy.
In the current study the link among the γ-hydroxybutyrate (GHB)/pentylenetetrazole (PTZ)-induced absence-like seizures and concomitant decreases in the core temperature, as well as electroencephalographic (EEG) activity during rewarming from deep hypothermia produced by a drug-free protocol were investigated. During the rewarming period after deep cooling, most Wistar rats suffered from bilaterally synchronous spike and waves with no or mild behavioral correlates. Spike and wave seizures were temperature-dependent and were initially registered when body temperature (Tb) reached 25-27°C, but mostly during the mild hypothermia of 0.3-1.3°C (Tb of 36.3-37.3°C). In chemical absence models, spike and wave discharges were also closely accompanied by mild systemic hypothermia, as both PTZ- and GHB-induced temperature decreases ranged from about 1-1.4°C respectively, together with EEG markers of absence activity. Thus, throughout the different experimental designs, the occurrence of spike and wave discharges was always related to a mild (0.3-1.4°C) decrease of Tb. Benzodiazepine diazepam as the GABAA-positive allosteric modulator and CGP 62349 as the selective antagonist of GABAB receptors were used to determine if their well-known anticonvulsant properties also affect hypothermia elicited by these drugs. Finally, during the course of spontaneous rewarming from deep hypothermia, another selective GABAB-blocking agent, CGP 35348, was used to elucidate if GABAB inhibitory system could be critically implicated in the generation of hypothermia-dependent spike and waves. Diazepam prevented both the PTZ-induced hypothermia and electrographic absence seizures, but these two beneficial effects did not occur in the GHB model. Even though diazepam delayed GHB-induced maximal temperature decrease, the GHB effects remained highly significant. The GABAB antagonist CGP 62349 completely prevented hypothermia as well as absence seizures in both chemical models. Likewise, spike and wave discharges, registered during the spontaneous rewarming from deep hypothermia, were completely prevented by CGP 35348. These findings show that systemic hypothermia should definitely be regarded as a marker of GABAB receptor activation. Moreover, the results of this study clearly show that initial mild temperature decrease should be considered as strong absence-provoking factor. Hypothermia-induced nonconvulsive seizures also highlight the importance of continuous EEG monitoring in children underg Topics: Animals; Anticonvulsants; Benzoates; Body Temperature Regulation; Cerebral Cortex; Diazepam; Epilepsy, Absence; Hypothermia; Male; Organophosphorus Compounds; Pentylenetetrazole; Rats; Rats, Wistar; Receptors, GABA-B; Seizures; Sodium Oxybate | 2013 |
GABA(B(1)) splice variant mRNAs are differentially affected by electroshock induced seizure in rats.
Receptor autoradiography with the high affinity antagonist radioligand [3H]CGP62349 and in situ hybridization with radiolabelled oligonucleotides were used to investigate GABA(B) receptor protein expression, and GABA(B(1)) mRNA splice variant (GABA(B(1a)) and GABA(B(1b)) levels, in brain sections from rats 4 h following a single electroshock-induced generalized seizure. Densitometric analysis indicated that GABA(B(1a)) mRNA levels were not significantly altered by an acute electroshock seizure, but that GABA(B(1b)) mRNA levels were significantly increased throughout the brain. GABA(B) receptor expression at this time point was unaffected by the seizure. The observed up-regulation of GABA(B(1b)) mRNA levels may imply increased importance of this splice variant in the regulation of further seizure activity. Topics: Animals; Autoradiography; Benzoates; Densitometry; Electroshock; In Situ Hybridization; Male; Oligonucleotides; Organophosphorus Compounds; Rats; Rats, Sprague-Dawley; Receptors, GABA-B; RNA, Messenger; Seizures | 2000 |