Biomedical subjects

C E Reigel

Publications and source records attributed to C E Reigel.

8 recordsLinked to original sources

PubMed1990

Decrease in hippocampal [3H]vinylidene kainic acid binding in genetically epilepsy-prone rats.

Specific [3H]vinylidene kainic acid binding to the kainate-sensitive subtype of glutamate receptor was studied in brain of 31-day-old non-epileptic Sprague-Dawley control and two colonies of genetically epilepsy-prone rats using in vitro autoradiographic techniques. At 37.5 nM [3H]vinylidene kainic acid, specific [3H]vinylidene kainic acid binding was reduced significantly by 18 and 22% in dorsal and ventral hippocampal formation stratum lucidum of 31-day-old genetically epilepsy-prone-9 rats compared with non-epileptic controls. Hippocampal [3H]vinylidene kainic acid binding was reduced in genetically epilepsy-prone-3 rats by 15 and 18%, but these reductions were not statistically significant. Saturation of [3H]vinylidene kainic acid binding studies indicated that the total number of ventral hippocampal [3H]vinylidene kainic acid binding sites was decreased by 21% in genetically epilepsy-prone-3 rats and 28% in genetically epilepsy-prone-9 rats. The reduction in ventral hippocampal [3H]vinylidene kainic acid binding in genetically epilepsy-prone rats resembles the reduction in ventral hippocampal [3H]vinylidene kainic acid binding sites observed in perinatal hypothyroid rats. As genetically epilepsy-prone rats are hypothyroid during the neonatal period, the reduction in hippocampal [3H]vinylidene kainic acid binding in the genetically epilepsy-prone rats may be a consequence of a hypothyroid-induced defect in the development or maturation of the hippocampal mossy fiber projection in genetically epilepsy-prone rats. An alternative hypothesis is that the putative occurrence of spontaneous limbic seizures in genetically epilepsy-prone rats may lead secondarily to a reduction in hippocampal [3H]vinylidene kainic acid binding sites.

Animals↗

PubMed1988

Responsiveness of genetically epilepsy-prone rats to intracerebroventricular morphine-induced convulsions.

The sensitivity to intracerebroventricular morphine-induced convulsions was determined in members of the severe seizure (GEPR-9) and moderate seizure (GEPR-3) colonies of genetically epilepsy-prone rats as well as in non-epileptic control rats. GEPR-9s were more sensitive to morphine-induced wet-dog shakes, rearing with bilateral forelimb clonus and generalized clonus than controls of GEPR-3s. GEPR-3s were less sensitive to morphine-induced wet-dog shakes and rearing with bilateral forelimb clonus than controls. Both high and extremely low doses of morphine in GEPR-9s elicited tonic extensor convulsions resembling the characteristic sound-induced convulsion of GEPR-9s. The results suggest that opiotergic systems may contribute to the pathophysiology of the seizure-prone condition in GEPR-9s. Further, differences in responsiveness of opiotergic systems in GEPR-3s and GEPR-9s may partially account for differences in seizure severity in the characteristic sound-induced seizures of these two types of GEPRs.

Animals↗

PubMed1988

Elevation of naloxone-sensitive 3H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats.

3H-Dihydromorphine (DHM) binding sites were measured in the brain of non-epileptic control and GEPR rats using in vitro autoradiographic techniques. The number of naloxone-sensitive 3H-DHM binding sites was increased 38-57% in the pyramidal cell layer of ventral hippocampal CA3 and Ca1 of GEPR-3 and GEPR-9 rats compared to non-epileptic controls. No significant differences in 3H-DHM binding were observed in dorsal hippocampal formation, lateral entorhinal cortex, lateral geniculate or cerebellum. The results suggest that an increase in the number of opioid receptors in ventral hippocampus of GEPR rats may be one factor contributing to the enhanced sensitivity of GEPR-9 rats to the proconvulsant effects of morphine.

Acoustic Stimulation↗

PubMed1988

Brain norepinephrine and convulsions in the genetically epilepsy-prone rat: sex-dependent responses to Ro 4-1284 treatment.

Seizure predisposition in the Genetically Epilepsy-Prone Rat (GEPR) is at least partially dependent on central nervous system noradrenergic deficits. We have previously shown that moderate seizure GEPRs (GEPR-3) experience an increase in seizure severity after receiving Ro 4-1284, a monoamine vesicle inactivating drug. We are now reporting the effect of this drug on severe seizure GEPRs (GEPR-9). Motives for this study were: (a) to determine the effects of further depletion of innately deficient monoaminergic stores on seizure latencies and (b) to investigate whether a previously documented seizure severity difference between the sexes is related to the defective monoaminergic system in these subjects. GEPR-9s with known seizure history were tested for latency to onset of running phase and convulsion 45 minutes after Ro 4-1284 or saline administration. Brain norepinephrine levels were also determined. Ro 4-1284 caused severe depletion of monoamines in all brain areas assayed in both sexes of GEPR-9s and also caused a reduction in the latencies for onset of running and convulsion. The drug-induced norepinephrine depletion across the brain areas surveyed was significantly greater in females than in their male littermates. These observations prompt us to postulate that noradrenergic neurons in female GEPR-9s are functionally different from those in males and that this difference is detected in the differential effectiveness of Ro 4-1284 between the two sexes. Also, the influence of gonadal hormones on seizure predisposition and on the neurochemical actions of Ro 4-1284 may be different in GEPR-9 males and females.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗

PubMedDate not supplied

Sex-specific distinctions in audiogenic convulsions exhibited by severe seizure genetically epilepsy-prone rats (GEPR-9s).

The severe seizure genetically epilepsy-prone rat (GEPR-9) is characterized by a broad-based seizure predisposition and is increasingly recognized as a useful model of epilepsy. When sound stimulated, members of the GEPR-9 colony exhibit complete tonic extensor convulsions. Female GEPR-9s appear to experience a higher frequency of more severe seizures than males when they are sound stimulated. The purpose of this report is to examine and document this observation. Convulsive behavior was evaluated in approximately 4400 GEPR-9s. Each of these animals was sound stimulated 3 times at weekly intervals. Audiogenic response score (ARS), latency to wild running and latency to convulsion were recorded for each animal in each of the 3 tests. For the first 2 weekly tests, females exhibited a significantly higher incidence of complete tonic convulsions, a significantly higher ARS and significantly shorter latencies to wild running and convulsions than did males. The significant differences in latencies persisted through the 3 tests, whereas an increase in the incidence of complete tonic convulsions among males led to a diminution of the differences between males and females in the other parameters. The possible underlying biochemical differences that are responsible for this sex difference in seizure severity are, as yet, unknown.

Acoustic Stimulation↗

PubMedDate not supplied

Audiogenic convulsions in moderate seizure genetically epilepsy-prone rats (GEPR-3s).

The moderate seizure genetically epilepsy-prone rat (GEPR-3) typically exhibits a generalized clonic convulsion upon acoustical stimulation. The purpose of this report is to document sex-specific distinctions in the seizure characteristics as well as the effect of prior seizure experience on sensitivity to acoustically induced seizures in members of the GEPR-3 colony. Convulsive behavior was evaluated in approximately 3300 GEPR-3s. Each of these animals was stimulated with sound 3 times at weekly intervals. Audiogenic response score (ARS), latency to the onset of wild running and latency to convulsion were recorded for each animal in each of 3 tests given at 1 week intervals. Statistical analysis revealed that compared to their male littermates, females exhibited significantly shorter latencies to onset of running and convulsion for the last of the 3 weekly tests. Also, in both sexes, a significantly higher incidence of clonic convulsions, an increase in audiogenic response scores and a reduction in latencies to running and convulsion were observed in each succeeding audiogenic stimulation test. The mechanism of this increased seizure facilitation with prior seizure experience may have at least some similarity to that of kindling. The factors responsible for sex-specific distinctions in seizure severity are unknown at the present time.

Acoustic Stimulation↗

PubMedDate not supplied

Ontogeny of sound-induced seizures in the genetically epilepsy-prone rat.

Seizure responsiveness of the adult genetically epilepsy-prone rat (GEPR) is well documented. Much less is known about the ontogeny to seizure activity in the GEPR. In the present study, members of the moderate seizure (GEPR-3) and severe seizure (GEPR-9) colonies were tested for susceptibility to sound-induced seizures at 11 different ages ranging from 13 to 45 days post partum. Running episodes first appeared in GEPR-3s at 15 days post partum. Clonic seizures first appeared in GEPR-3s and GEPR-9s at 15 and 16 days post partum, respectively. Seizure incidence reached 100% by post partum day 21 in both colonies. GEPR-3s exhibited a 100% incidence of their characteristic clonic seizure at day 21. GEPR-9s exhibited a 77.3% incidence of clonic seizure and a 22.7% incidence of their adult characteristic tonic seizure at day 21. Tonic seizures first appeared in GEPR-9s at day 18 and increased in incidence over time reaching 100% by day 45. Two unexpected findings occurred in GEPR-3s. First, secondary rearing seizures were detected in all GEPR-3s exhibiting clonic seizures between day 16 and 21. Second, GEPR-3s exhibited a transient susceptibility between 19 and 27 days post partum to the more severe tonic seizures characteristic of adult GEPR-9s. Peak incidence of tonic seizures in GEPR-3s was 70%, occurring at day 23. The adult GEPR-3 pattern of 100% incidence of clonic seizures was restored by day 45.

Acoustic Stimulation↗

PubMedDate not supplied

Neurobiology of seizure predisposition in the genetically epilepsy-prone rat.

Seizure predisposition in the genetically epilepsy-prone rat (GEPR) is innately determined and these animals exhibit consistent and reproducible convulsive patterns. This epilepsy model is made up of 2 independently derived colonies of animals with each exhibiting a characteristic convulsive pattern. In response to a standardized acoustic stimulus, GEPR-3s exhibit moderate or clonic convulsions and GEPR-9s exhibit more severe tonic extensor convulsions. Besides exhibiting convulsions in response to sound stimulation, some GEPRs experience spontaneous and hyperthermic seizures. They are also abnormally sensitive to a number of seizure provoking stimuli that produce seizures in normal animals. The neurochemical basis for the seizure predisposition in GEPRs is increasingly well understood. Abnormalities in central nervous system norepinephrine and serotonin are widespread and may play a prominent role in regulation of seizures in the GEPR. Amino acid neurotransmitter systems are less well defined in the GEPR but abnormalities exist and may be, along with other documented deficiencies, responsible in part for the seizure predisposition that is characteristic of GEPRs.

Acoustic Stimulation↗