Audiogenic Seizure Susceptibility Research Articles

Psychoactive compounds and audiogenic seizure susceptibility

The purpose of these experiments was to gain comparative information about psychoactive compounds on experimental convulsions, a phenomenon that has been used as an index of CNS excitability. LSD, mescaline, d- and 1-amphetamine, cocaine and morphine were all effective in blocking audiogenic seizure susceptibility. None of the compounds were effective in blocking the priming of a non-susceptible strain of mice. This latter finding differentiates these compounds from Δ 9-tetrahydrocannabinol which has been previously reported to block priming.

Effect of priming and tympanic membrane destruction on development of audiogenic seizure susceptibility in [formula omitted] mice

Induction of audiogenic seizure susceptibility was studied in rmBALB c mice by bell priming or by destruction of their tympanic membranes. Bell priming was not so effective at 14 days of age as at 21 days. However, a high incidence of seizure was induced in the 14- and 21-day-old mice by rupturing their tympanic membranes; the incidence and severity of seizures thus induced was higher in the 14-day-old group. The rate of development of seizure susceptibility was also faster in the younger mouse. The results provide further support for the hypothesis that auditory deprivation resulting from priming is a critical factor for development of the priming effect. They also indicate that susceptibility of the cochlea to stimulation damage and the maturational stage of the mouse may influence the effect of priming for audiogenic seizures.

Effects of monaural and binaural auditory deprivation on audiogenic seizure susceptibility in [formula omitted] mice

Mice of the BALB c strain were divided into three groups at 20 ± 1 days of age. One group was deprived binaurally of auditory input by destroying the tympanic membrane bilaterally. A second group was monaurally deprived of auditory input by unilateral tympanic membrane destruction. The third group of control animals was sham-operated and the membranes were left intact. At 27 ± 1 days of age, all three groups of mice were tested behaviorally for audiogenic seizures. On exposure to the loud sound, a majority of the auditory-deprived animals of both operative groups exhibited audiogenic seizure reactions, but none of the sham-operated controls showed seizure behavior. These findings lend support to the hypothesis that induction of seizure susceptibility is a result of auditory deprivation.

9 -Tetrahydrocannabinol effect on audiogenic seizure susceptibility.

Mice, normally not susceptible to audiogenic seizures, can be made susceptible by exposing the animal to a loud auditory stimulus (priming) and then retesting the same animal at a later time (retest). δ 9-Tetrahydrocannabinol (THC) was found to decrease susceptibility when administered either prior to priming or prior to retest. This decrease in susceptibility was dependent upon both time and dose. The effectiveness of THC in blocking seizures when administered before priming points to a relatively unique action of this compound. In general, it appears the THC is active at loci involved in predetermining convulsive states precipitated by auditory stimuli.

5-Hydroxytryptophan reversal of reserpine enhancement of audiogenic seizure susceptibility in mice

Increased sensitivity to audiogenic seizures by reserpine was antagonized by 5-hydroxytryptophan (5HTP). The antagonism was dependent upon the conversion of 5HTP to 5 hydroxytryptamine (5HT) in brain since blockade of both cerebral and extracerebral decarboxylase prevented the 5HTP effect, whereas selective blockade of extracerebral decarboxylase did not affect the 5HTP antagonism. Increased seizure susceptibility occurred when brain concentrations of 5HT were decreased, while decreased susceptibility occurred when brain concentrations of 5HT were elevated. 5HTP did not alter norepinephrine or dopamine concentrations in brain. The results of this study indicate that 5HT plays a role in modulating audiogenic seizure susceptibility.

Audiogenic seizure susceptibility of rats X-irradiated in utero late in pregnancy

Sherman strain rats exposed in utero to a maternal whole-body dose of 250 r of X-radiation, on Day 17, 18, or 19 of pregnancy, were tested for their susceptibility to sound-induced seizures at a median age of either 256, 266, or 322 days. There was no significant difference among the three prenatally X-irradiated groups or among the control groups, or between any X-irradiated group and its comparably aged control series, or between all X-irradiated animals grouped together and all control animals, in the number of rats displaying running attacks, or seizures, or both. Nor did the latency times (intervals between onset of bell and running attack) of prenatally X-irradiated reactors differ significantly from those of control reactors. No sex difference in susceptibility to sound-induced running attacks or seizures was found among the irradiated or control animals, or between them. The present findings are in line with and, indeed, complement those derived earlier from similarly treated animals tested for seizure susceptibility at a median age of 21 1 2 months. Apparently, the central neural changes produced in the rat by exposure in utero to maternal X-ray irradiation late in pregnancy (described by us and by others), do not collectively predispose or significantly affect the susceptibility of survivors to sound-induced seizures, at least at the ages when this was studied. Data supporting the reliability of some earlier reported age-seizure susceptibility relationships in the normal (Sherman) rat were also noted.

Circadian rhythms and seizure susceptibility: Effects of manipulations of light cycles on susceptibility to audiogenic seizures and on levels of 5-hydroxytryptamine and norepinephrine in brain

Susceptibility to audiogenic seizures was determined in 26-day-old DBA/2J mice raised under either normal (LD) or reverse-cycle (DL) lighting conditions. Reverse-cycle lighting conditions completely reversed the circadian rhythm of susceptibility to audiogenic seizures in these mice. In another experiment, mice were placed into either LD, DL, complete light (LL) or complete dark (DD) conditions at noon of either Days 21, 23, 25 or 26. These animals were then tested for susceptibility to audiogenic seizures at either 1700 or 2000 hr of Day 26. Reverse-cycle lighting conditions for 5 days almost reversed the audiogenic seizure susceptibility pattern, and both DD and LL conditions sharply increased susceptibility to audiogenic seizures. In a third experiment, DBA/2J mice were placed into either LD, DL, DD or LL conditions at noon of Day 21 and sacrificed at 1700 hr on Day 26. Levels of 5-hydroxytryptamine and norepinephrine were measured in cortex, diencephalon and brain stem of these mice. Increased susceptibility to audiogenic seizures was found to be directly related to lower levels of 5-hydroxytryptamine and norepinephrine in brain. The relation between susceptibility to audiogenic seizures and levels of these biogenic amines in brain is discussed.

Susceptibility to audiogenic stimuli induced by hyperbaric oxygenation and various neuroactive agents

The effects of agents, or combinations of agents, which are known to modify the pattern of brain activity or brain levels of neurohumoral agents on reversible audiogenic seizure susceptibility induced by hyperbaric oxygenation (HPO) at six atmospheric pressure (ATA), were studied in rats. A precursor of catecholamine, dl-3,4-dihydroxyphenylalanine (DOPA), and a precursor of serotonin, dl-5-hydroxytryptophan (5-HTP), showed slight intensification and some inhibition, respectively. The tyrosine hydroxylase inhibitor, dl-α-methyl- p-tyrosine (α-MPT) slightly decreased the susceptibility and dl-p-chlorophenylalanine (PCPA), the tryptophan hydroxylase inhibitor, slightly intensified the susceptibility. Combined administration of these agents produced a maximal degree of protection against the development of audiogenic susceptibility in this series. Atropine and eserine produced some protection and a slight intensification, respectively. Reserpine, a depletor of catecholamine and serotonin, produced a slight accentuation at 20 min and a subsequent decrease at both 1 hr and 10 hr. When DOPA, 5-HTP, or both DOPA and 5-HTP, were given to the reserpinized animals at 10 hr, prominent intensification of the susceptibility along with a high mortality were observed. The data suggest that the availability of free but not bound serotonin and catecholamine are responsible for the modulation of the HPO-induced audiogenic seizure susceptibility. The finding is consistent with our view that site or sites of HPO action underlying this transient susceptibility may be located at the synapse.

Dopa reversal of reserpine enhancement of audiogenic seizure susceptibility in mice.

Increased sensitivity to audiogenic seizures induced by reserpine was antagonized by dopa. The antagonism was dependent upon the conversion of dopa to dopamine in brain since blockade of both cerebral and extracerebral decarboxylase prevented the dopa effect, whereas blockade of extracerebral decarboxylase only did not affect the dopa antagonism. Increased seizure susceptibility occurred when brain levels of NE and DA were significantly lowered, while decreased susceptibility was found when brain levels of DA were significantly elevated. The results of this study indicate that dopamine plays a role in protection against audiogenic seizures in mice.

Reversible audiogenic seizure susceptibility induced by hyperbaric oxygenation

Hyperbaric oxygenation at 6 absolute atmospheric pressure (ATA) produced a reversible audiogenic seizure susceptibility with marked circadian alteration in genetically “nonsensitive” rats. We postulate that the site of hyperbaric oxygen action underlying this transient susceptibility may be at the synapse.

Audiogenic seizure susceptibility of rats X-irradiated in utero during first one-third of pregnancy

Groups of Sherman rats exposed in utero to a maternal dose of 250 r of X-radiation, during the first one-third of pregnancy, were tested for susceptibility to sound-induced seizures at a median age or 175, 230, or 258 days. There was no significant difference between any irradiated group and control animals of comparable age in either number of running attacks or seizures. A need for caution in generalizing from these findings to other samples of rats, tested at equivalent ages, has been noted. The suggestion by others of decreased susceptibility in 4-month-old offspring of Sprague-Dawley rats exposed to lower doses of X-radiation, on gestational day 5 or 10, was found to be inadequately supported by their data. Well-known differences in audiogenic seizure susceptibility in relation to age in normal animals, evident in the present study, underscore the importance of the age-at-testing variable in evaluating susceptibility in the prenatally X-irradiated rat, as well as the need for longitudinal studies in making that determination. Beyond its special consideration in seizure studies, the variable of test age appears to be of fundamental importance in elaborating the functional consequences of prenatal X-irradiation. The present report reduces the already limited number of behavioral changes said to occur in rats surviving X-irradiation during the preorganogenetic period. In view of the absence of light microscopic evidence of damage to their brains, a search for functional alterations in such animals would seem to be particularly challenging.

Circadian alteration of audiogenic seizure susceptibility in rats

Genetically determined audiogenic seizure susceptibility in Wistar albino rats showed distinct rhythmicity with its increase and decrease during night and day, respectively. This rhythmicity is apparently regulated by light since its trend can be readily reversed by artificially reversing the illumination pattern of day-night schedule in their colony. This is best observed in rats which are arbitrarily classified as nonsensitive with no response to six day-time audiogenic stimulations on alternate days.

A new genetic locus mapped from behavioral variation in mice: audiogenic seizure prone (ASP).

Audiogenic seizure susceptibility to the initial presentation of intense sound was studied in generations of mice derived from the susceptible DBA/2J and the resistant C57BL/6J inbred strains. The experimental results led to the detection, location, and position of a new genetic locus affecting behavior in mice. The locus is designatedasp (audiogenic seizure prone), and the pattern of inheritance for high seizure risk is recessive. Evidence for the mapping ofasp results from the following experimental findings: (1) frequencies of seizures for each of six segregating generations obtained by crossing C57BL/6J and DBA/2J conformed to expectations based upon a single locus model of genetic inheritance; (2) theasp-locus is loosely linked to theb-locus and thus resides on Linkage Group VIII of the mouse; (3) linkage relationships betweenasp and other named mutations on LG VIII, pintail (Pt),misty (m), brown (b), and autosomal glucose-6-phosphate dehydrogenase (Gpd-1), indicate that the position of theasp-locus is towards the centromeric end of the chromosome. The order of loci isasp-b-Pt-Gpd-1; (4) no linkage was observed betweenasp and thed-locus of Linkage Group II. These experiments illustrate that new genetic loci, whose allelic alternatives exert major effects on chosen behavioral characters, can be identified and mapped in a directed search.

Susceptibility to audiogenic seizure induced by thiosemicarbazide

Rats, cats, and monkeys were subjected to audiogenic stimuli after the administration of thiosemicarbazide (TSC). The treated rats responded to audiogenic stimulation with episodic running behavior (ERB) with or without convulsion (C), the most effective dosage being 4.4 mg/kg. In rats, the pattern of audiogenic response in genetically sensitive rats and TSC-treated nonsensitive rats was indistinguishable. Treatment of audiogenic-sensitive rats with TSC produced some accentuation of audiogenic response. Cats responded to audiogenic stimulation with ERB, ERB + C, C + ERB, or C alone. In addition, entirely independent and spontaneous convulsion was observed. The threshold dosage was 7.0 mg/kg. Monkeys responded to audiogenic stimulation with C, motor excitement followed by C, or C followed by repetitive vocalization or motor excitement. Monkeys also showed independent and spontaneous C. In cats and monkeys, unlike methionine sulfoximine-induced episodic behavior, spontaneous C and audiogenic response were not mutually exclusive. Although some electrographic evidence of preferential involvement of temporal lobe structures was obtained, no discernible seizure discharge was observed in any brain structures explored during ERB or restlessness induced by audiogenic stimulation. In spite of some interspecies response variation it was conclusively shown that TSC induces transient audiogenic seizure susceptibility in rats, cats, and monkeys.

Effects of levels of audiogenic-seizure susceptibility on endocrine function of rats

The present study searched for relationships and correlations between the respective level of individual audiogenic-seizure susceptibility patterns and metabolic and endocrine differences in seizure-susceptible vs. resistant animals. Immature, female Wistar rats were subjected to high intensity alarm bell stress (115–120) db and scored for variations in intensity and frequency of behavioral reactions (i.e., wild-running seizures and convulsions, for 5 min, at 4 equally spaced occasions during a 2-week testing period. Recording of fecal pellet counts, urine excretion volumes, O 2 consumption and subsequent organ weight differences noted after autopsy at the end of a following 2-week period, revealed significant increases in fecal and urinary elimination rates of the seizure-susceptible rats; significant increases in the relative adrenal weights were, likewise, accompanied by corresponding increases in adrenal ascorbic acid content per gland and significant decreases in the thymus weights of the seizure-susceptible rats. The greatest percent differences and degree of changes were noted in the most highly susceptible rats which suffered wild-running seizures and convulsive attacks at all 4 testing trials. The addition and inclusion of less susceptible animals in the group analyses consistently caused a diminution in the level of differences between the most highly susceptible group and the resistant-control group. The range and differences in adrenal, thymus and ascorbic acid values of the most susceptible rats (Group 1) vs. total susceptible (Group 1, 2 and 3) vs. the seizure-resistant control group suggest a direct relationship of adrenal function to the level of seizure susceptibility. The difference in fecal pellet counts and urine excretion values, similarly afforded evidence of alteration in food metabolism and excretory reflexes of the susceptible animals.

Audiogenic seizure susceptibility induced in C57BL-6J mice by prior auditory exposure.

Pronounced susceptibility to audiogenic seizures was produced in highly resistant C57B1/6J mice after earlier exposure to a loud electric bell. There is a critical period between initial acoustic presentation and subsequent testing for susceptibility; this suggests a minimum age and a minimum lapse of time during which this priming is effective.

Audiogenic Seizure Susceptibility Induced in C57B1/6J Mice by Prior Auditory Exposure

Pronounced susceptibility to audiogenic seizures was produced in highly resistant C57B1/6J mice after earlier exposure to a loud electric bell. There is a critical period between initial acoustic presentation and subsequent testing for susceptibility; this suggests a minimum age and a minimum lapse of time during which this "priming" is effective.

Auditory sensitivity in mice: Peromyscus and Mus musculus

Summary Auditory evoked potentials from the posterior colliculus were used to measure auditory threshold in Peromyscus leucopus, P. boylii , feral Mus musculus and strain BALB/cJ and DBA/2J laboratory mice. Moderate Nembutal anaesthesia had no consistent effect on the shape, amplitude, latency or threshold of the evoked potentials. Peromyscus boylii and young P. leucopus appear to have a high frequency sensitivity similar to that of the bat Myotis lucifugus up to about 70 kHz. The feral Mus musculus were more sensitive to higher frequencies than any of the laboratory mice tested, having lowest thresholds at about 20 kHz. The high frequency sensitivity of strain DBA/2J mice declines rapidly with age, which probably explains their loss of audiogenic seizure susceptibility with age. Mice of strain BALB/cJ were most sensitive to frequencies of about 12 kHz. Their high freuency sensitivity tends to decline with age, but not as rapidly or consistently as in strain DBA/2J mice. The high incidence of sensory deficits in laboratory mice, and the difficulty of detecting them, can confound the results of behavioural studies on inbred laboratory mouse strains.

Albinism and audiogenic seizures in the mouse

Albino (cc) and non-albino (CC or Cc) mice were tested for audiogenic seizure susceptibility beginning at all of the ages from day 14 to day 21 postpartum. At every starting age the onset of first seizure was later for the albino genotype. The latency measures and day of death indicate, however, that the initial retardation is overcome by a faster subsequent development.

Effect of tranquilizing drugs on postnatal behavior

Chlorpromazine 6 mg/kg and reserpine 0.1 mg/kg were given subcutaneously to pregnant albino rats on days 4–7 of gestation in order to investigate in more detail previous reports of long-term behavioral modification of offspring by these drugs. Reserpine did not cause significant differences from controls. Chlorpromazine was shown to decrease motor activity and increase audiogenic seizure susceptibility in offspring. Those animals below average in weight and in motor activity were most likely to exhibit convulsive responses. These associated factors are interpreted as representing an altered behavioral complex. These abnormal responses were found in some animals of every chlorpromazine litter. No histological differences in the brains and no differences in susceptibility to amphetamine toxicity could be demonstrated in offspring of chlorpromazine-treated mothers.