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Genetics of audiogenic seizures: I. Relation to brain serotonin and norepinephrine in mice
Life Sciences Vol. 4, pp, 2345-2351, 1965 . Printed in Great Britain
- Pergamon Press Ltd.
CENSTICS OF AUDIOCRNIC S=IZURKS : I . RELATION TO BRAIN SEROTOKIN Alm NORRrINKPHR1 M IN MICS 1 Kurt Schlesinger, William Boggan Department o£ Psychology, University of North Carolina, Chapel Hill aid Daniel Z . headman Laboratory of Psychopharsacology, Department of Psychiatry, ° Yale University Scbool of Medicine
(Received 31 August 1965) Inbred strains of mice are known to differ widely in their responses to loud high frequency sounds ; some strains, particularly dilute strains, (d/#), are extremely susceptible to audiogenic seizures (1,2) .
Susceptibility to
audioganic seizures is known also to be a function of age and is particularly high in young animals (3) .
The mechanism (s) underlying susceptibility to
audiogenic seizures in d/d mice is unknown although several hypotheses have been advanced (4) .
Coleman (5), for ezample, has found 1d mice deficient in
phanylalanine hydrozylase activity and has shown that this leads to the accumulation of abnormal phanylalanins metabolites such as phenylacetic acid .
In-
asmuch a . phanylecetic acid inhibits decarboxylating reactions (6,7), Coleman has speculated that d/d mice might have lower game-minobutyric acid (CABA), norepinephrine (NE), and serotonin (5-HT), levels and that this, in turn, might account for susceptibility to audiogenic seizures . The purpose of the present experiment was twofold :
Piret, to determine
susceptibility to audiogenic seizures in mice of different strains at different ages .
Second, to determine NS and 5-HT levels in mice of different strains
at different ages, in an attempt to correlate seizure susceptibility with the levels of these compounds in brain . This investigation was supported by a research grant MH03363-06 from the National Institute of Mental Health . We wish to thank Mr . Stephen Pachl and Mr . Karlis Rositis for technical assistance .
2345
2346
Vol . 4, No . 24
AUDIOGEliIC SEIZUZS Methods Subjects :
For the first experiment 75 mice from each of 3 groups were
These groups were dilute strains DBA/2J Q/!j), son-dilute strains
used :
C57BL/6J (D/P), and the Flhybrid between these strains (D/!j) .
Seizure testing
was done when these animals were 14, 21, 28, 35, and 42 days of age .
For the
second experiment mice of the same 3 groups were used and chemical determinations were made at 14, 21, 28, 35, and 42 days of age .
The origin and degree
of inbreeding of these mice has been described (8) . Procedures :
Animals were tested using the method described by Fuller (9) .
Animals were taken from their home cages one at a time, brought to another room, placed in a large chromatography jar, and given 30 sec . t o adapt .
A 5"
electric bell was mounted over the top of the jar and was sounded for 90 sec . The animals were observed during this period and records were made of the wild running phase, clonic, and tonic seizures . Chemical analyses :
Animals were sacrificed by decapitation, the brains
were rapidly removed, weighed to the nearest 0 .1 g, and quickly frozen on dry ice .
The tissue was delivered for chemical analyses under code number .
tissue was obtained between 8 and 9 a .m . and age, was random .
All
Order of chemical analyses, by strain
Brains 5-BT and NS determinations were made on whole
brain homogenates by fluorescence spectrometry as described by Mead and Finger (10) . Results Table 1 is a summary of seizure incidences obtained with DBA/2J, C57BL/6J, and B6D2F1 mice of various ages .
The data are presented for the wild running
phase (a behavior which usually but not always precedes the onset of the seiz ure), and the incidence of both the clonic and tonic seizures .
The data ill-
ustrate quite clearly both the genetic and developmental determinants of seizure susceptibility .
It is apparent that DBA/2J mice are more susceptible than
either C57BL/6J or B6D2F1 mice .
If the most severe type of seizure, i .e ., the
Vol . 4, No . 24
full clonic-tonic seizure,
AUDIOGENIC SEIZURES
2347
is used as an index of susceptibility, DBA/2J mice
show an incidence of 87% at 21 days of age as contrasted with a 20% incidence for the F1 hybrid and a 0'L incidence for the C57BL/6J animals .
Audiogenic
seizures also depend on the age of the animals at the time of testing.
With
full clonic-tonic seizures as an index the DBA/2J mice are swat susceptible at 21 days of age with an 87% risk .
Seizure incidence is only 13% one week
before and one week after this period .
The same devmlopmental pattern was
obtained for the F1 hybrid whereas C57BL/6J mice never showed the full clonictonic pattern. Table 2 summarizes brain weight, and brain 5-HT and NE levels in these 3 groups of mice at various ages .
Data are presented for total and specific
(per gm wet weight) 5-HT and HE levels .
These data illustrate that the differ
ences in both 5-HT and NE leve1e between the groups are maximal at 21 days of age which corresponds to tho period of maximal seizure susceptibility for the DBA/2J mice .
The differences in total brain 5-HT between DBA/2J and C57BL/6J
mice are approximately 32% at 21 days of age and are statistically significant (t-4 .24 ; df - 12 ; R ,< .01) ; the value for the Fl hybrid is intermediate .
The
differences in total brain NE between DBA/2J and C57BL/6J mice is approximately 44x at 21 days of age and is statistically significant (t - 6 .41 ; df - 12 ; l' <.01) ; the value for the F1 hybrid is intermediate . Brain weights increase slightly from 14 to 42 days of age in all groups . At 21 days of age, however, brain weights of DBA/2J and C57BL/6J mice are not different . Discussion These data agree with those reported by previous investigators in two respects :
first, the importrnce of genetic factors in seizure susceptibility
and second, that the age of the animals at the time of testing is of great importance in seizure susceptibility .
DBAi2J mice were found to be more suscep-
Vol. 4, No . 24
AUDIOGENIC SEIZURES
2348
TABLE 1 Susceptibility to Audiogenic Seizures as a Function of Age
Strain
Age (in days)
if
Seizure Susceptibility
Wild -Running
Clonic
Tonic
27% 87% 40% 40% 7%
13% 87% 13% 7% 0%
DBA/2J DBA/2J DBA/2J DBA/2J DBA/2J
14 21 28 35 42
15 15 15 15 15
73% 100% 87% 67% 27%
C57BL/6J C57BL/6J C57BL/6J C57BL/6J C57BL/6J
14 21 28 35 42
15 15 15 15 15
27% 7% 0% 13% 0%
0% 0% 0% 0% 0% .
0% 0% 0% 0% 0%
B6D2F1 B6D2Fl B6D2F1 B6D2F1 B6D2F1
14 21 28 35 42
15 15 15 15 15
Ox So% 87% 60Z 13x
Ox 20% Ox 13x 0%
20x Ox 7% 0%
tible than C57BL/6J nice and the Fl hybrid was intermediate in susceptibility, although closer to the non-susceptible parent .
The critical period for max-
imum seizure susceptibility, in DBA/2J nice, was quite short (approximately 6 days) ; clonic-tonic seizure incidence was 87% at 21 days of age but only 13% at 14 and 28 days of age . Different investigators have suggested different modes of inheritance for audiogenic seizures ranging from single gene, two gene, to polygenic modes of inheritance (11) .
The results of the present study (Table 1) indicate that
same of the discrepancy may depend on the particular measure used as an index of seizures, i .e ., whether the wild running phase or only full clonic-tonic seizures are used as indices .
Another factor determining the outcome of such
genetic experiments may be the age chosen to measure susceptibility . experiments are in progress to elucidate some of these factors.
Breeding
DBA/2J 7 B6D2Fl 6 C57BL/6J 7
6 DRAW B6D2Fl 7 C57BL/6J 7
DBA/23 6 B6D2Fl 7 C57BL/6J 7
DRAW 6 B6D2F1 6 C57BL/6J 5
21 days
28 days
35 days
42 days " "
"
"
"
"
"
"
DBA/2J 6 36D2Fl 6 C57BL/6J 6
14 days
N
Strain
Age
0 .390 0 .434 0 .421
0 .376 0 .3% 0 .389
0 .418 0 .402 0 .398
0 .328 0 .413 0 .359
0 .340 0 .374 0 .371
±0 .14 +0 .03 +0 .10
±0 .02 ±0 .01 ±0 .01
+0 .27 ±0 .01 ±0 .03
±0 .02 +0 .01 ±0 .21
+0 .15 +0 .01 +0 .17
Brain Weights (8") z s .d .
262 282 255
229 246 231
214 230 235
155 201 228
154 145 185
±33 ±27 +20
+14 +10 ±53
±38 ±15 ±30
±33 + 9 ±10
±25 +18 +19
Total 5H-T (mug) s .d . =
683 652 605
612 622 588
593 574 589
466 485 638
456 388 498
+62 ±74 +46
+43 ±34 ±94
±93 +39 +82
±104 +29 ±28
±88 +46 +54
5-BT Total (2mg/g) x s .d .
212 208 231
163 188 189
152 196 185
105 167 189
121 117 125
+15 +39 +14
±51 +14 ±45
±25 ±23 +55
±31 +17 ±16
±25 +11 +13
Total NE (-s) i s .d .
±73 +47 ±36
±17 +24 +36
555 480 548
+41 ±33 +25
438 ±146 474 ±14 481 ±81
427 +82 489 +60 465 ±144
317 397 526
365 312 337
NE Total (aug/g) x s .d .
Brain Serotonin and Norepinephrine Levels as a Function of Strain and Age
H 0
H
0
Z
AUDIOGENIO SEIZUMS
2350
Vol. 4, No . 24
When genetic and developmental differences in seizure susceptibility were established it was easier to attempt to correlate levels of 5-HT and WE with seizure incidence .
If 5-HT and NE are involved in determining seizure suscep
tibility then we would expect to find differences in levels of these compounds but only at ages at which significant differences in seizure incidence are found .
These data suggest that 5-HT and NE are important in determining sus-
ceptibility to audiogenic seizures since lower levels of these amines in DBA/ 2J mice were found only at the time of maximum seizure risk . The exact role of 5-HT and HE in determining audiogenic seizure susceptibility remains to be explained .
Further, the biochemical mechanism by which
levels of these amines are lowered in DBA/2J mice at 21 days of age is as yet unspecified .
Coleman (5) has suggested that this might be due to the accumul-
ation of abnormal phenylalanine metabolites, a .g ., phenylacetic acid in animals with low phenylalanine hydroxylase activity such as DBA/2J mice .
Phenylacetic
acid has been implicated as an inhibitor of 5-HTP decarboxylase (6) but it is generally accepted that decarbozylation is not the rate-limiting step in the anabolism of 5-HT and NE (12,13) .
Another possible mechanism for the low le-
vels of 5-HT and NE found in DBA/2J mice are the high levels of circulating phenylalanine which might be found in animals with low phenylalanine hydroxylase activity ; McKean, Schanberg and Giarman (14) have shown that high levels of blood phenylalanine inhibit the transport of 5-hydroxytryptophan into brain and that this leads to reduced levels of 5-HT in this organ .
Experiments are
in progress which will attempt to elucidate the mechanism underlying the reduced levels of'15-HT and NE seen in DBA/2J mice at the time of maximal seizure susceptibility . Summary Audiogenic seizure susceptibility was determined in DBA/2J, C57BL/6J, and B6D2F1 mice of various ages .
Audiogenic seizure susceptibility was great-
est in DBA/2J mice which showed an 87% incidence of clonic-tonic seizures at
AUDIOGENIC SEIZUMS
Vol . 4, No . 24
2351
21 days of age ; seizure incidence in this strain was only 13% at 14 and 28 days of age .
B6D2Fl animals staved a lover seizure risk but a similar development-
al pattern.
C57BL/6J mice were resistant to sudiogenic seizures .
Brain levels
of 5-HT and NE were determined in these same groups of mice at the same developmental ages .
Significant differences in 5-HT (32X) and NE (44x) were found
between DBA/2J and C57BL/6J mice ; the values for DBA/2J mice were lower and and the values for the B6D2F1 mice were intermediate .
The differences were
found only at 21 days of age which corresponds to the time of masiul seizure susceptibility in DBA/2J mice . References J. L . FULLER and ELIZABETH WILLIAM, Froc . Nat . Acad . Sci . Wash ., (1951) .
37, 349
2.
DOROTHY S. MILLER, B . E . GIOSBURG and MILDRED A. POTAS, Genetics , 37,605 (1952) .
3.
J. L . FULLER, AU . N. Y . r:cad . Sei., 96, 199 (1962) .
4.
L. G . ABOOD and R. W. GERARD, in Biochemistry of the Developing Nervous System , Academic Press, edit . by H. Waelsch (1955) .
5.
D. L. COLEMAN, Arch . Biochem. Biophy . , 91, 300 (1%0) .
6.
M. SANDLER and H. CLOSE, Lancet , 7098 (II) , 317 (1959) .
7.
A. HANSON, Naturwissenschaften, 45, 423 (1958) .
8.
G. E. JAY, JR., in Methodology in Mammalian Genetics , Holden-Day Inc ., edit . by W . J. Burdette (1963) .
9.
J. L. FULLER, Rec. Genet. Soc . Amer ., 18, 86 (1949) .
10 .
J . MEAD and K. FINGER, Biochem. Pharmacol ., 6, 52 (1%1) .
11 .
J. L. FULLER and W. R . THOMPSON, Behavior Genetics , John W. Wiley and Sons, (1960) .
12 .
T . NAGATSU, M. LEVITT and S . UNDENFRIEND, J. .Biol . Chem . , 239, 2910 (1964) .
13 .
S . SPECTOR, A. SJOERDSMA and S. UDENFRIEND, J. Pharm. Exp . Therap ., 147, 86 (1965) . C . M. MCKEAN, S. M. SCHAMBERG and N. J. GIARMAN, Science, 137, 604 (1%2) .
- Pergamon Press Ltd.
CENSTICS OF AUDIOCRNIC S=IZURKS : I . RELATION TO BRAIN SEROTOKIN Alm NORRrINKPHR1 M IN MICS 1 Kurt Schlesinger, William Boggan Department o£ Psychology, University of North Carolina, Chapel Hill aid Daniel Z . headman Laboratory of Psychopharsacology, Department of Psychiatry, ° Yale University Scbool of Medicine
(Received 31 August 1965) Inbred strains of mice are known to differ widely in their responses to loud high frequency sounds ; some strains, particularly dilute strains, (d/#), are extremely susceptible to audiogenic seizures (1,2) .
Susceptibility to
audioganic seizures is known also to be a function of age and is particularly high in young animals (3) .
The mechanism (s) underlying susceptibility to
audiogenic seizures in d/d mice is unknown although several hypotheses have been advanced (4) .
Coleman (5), for ezample, has found 1d mice deficient in
phanylalanine hydrozylase activity and has shown that this leads to the accumulation of abnormal phanylalanins metabolites such as phenylacetic acid .
In-
asmuch a . phanylecetic acid inhibits decarboxylating reactions (6,7), Coleman has speculated that d/d mice might have lower game-minobutyric acid (CABA), norepinephrine (NE), and serotonin (5-HT), levels and that this, in turn, might account for susceptibility to audiogenic seizures . The purpose of the present experiment was twofold :
Piret, to determine
susceptibility to audiogenic seizures in mice of different strains at different ages .
Second, to determine NS and 5-HT levels in mice of different strains
at different ages, in an attempt to correlate seizure susceptibility with the levels of these compounds in brain . This investigation was supported by a research grant MH03363-06 from the National Institute of Mental Health . We wish to thank Mr . Stephen Pachl and Mr . Karlis Rositis for technical assistance .
2345
2346
Vol . 4, No . 24
AUDIOGEliIC SEIZUZS Methods Subjects :
For the first experiment 75 mice from each of 3 groups were
These groups were dilute strains DBA/2J Q/!j), son-dilute strains
used :
C57BL/6J (D/P), and the Flhybrid between these strains (D/!j) .
Seizure testing
was done when these animals were 14, 21, 28, 35, and 42 days of age .
For the
second experiment mice of the same 3 groups were used and chemical determinations were made at 14, 21, 28, 35, and 42 days of age .
The origin and degree
of inbreeding of these mice has been described (8) . Procedures :
Animals were tested using the method described by Fuller (9) .
Animals were taken from their home cages one at a time, brought to another room, placed in a large chromatography jar, and given 30 sec . t o adapt .
A 5"
electric bell was mounted over the top of the jar and was sounded for 90 sec . The animals were observed during this period and records were made of the wild running phase, clonic, and tonic seizures . Chemical analyses :
Animals were sacrificed by decapitation, the brains
were rapidly removed, weighed to the nearest 0 .1 g, and quickly frozen on dry ice .
The tissue was delivered for chemical analyses under code number .
tissue was obtained between 8 and 9 a .m . and age, was random .
All
Order of chemical analyses, by strain
Brains 5-BT and NS determinations were made on whole
brain homogenates by fluorescence spectrometry as described by Mead and Finger (10) . Results Table 1 is a summary of seizure incidences obtained with DBA/2J, C57BL/6J, and B6D2F1 mice of various ages .
The data are presented for the wild running
phase (a behavior which usually but not always precedes the onset of the seiz ure), and the incidence of both the clonic and tonic seizures .
The data ill-
ustrate quite clearly both the genetic and developmental determinants of seizure susceptibility .
It is apparent that DBA/2J mice are more susceptible than
either C57BL/6J or B6D2F1 mice .
If the most severe type of seizure, i .e ., the
Vol . 4, No . 24
full clonic-tonic seizure,
AUDIOGENIC SEIZURES
2347
is used as an index of susceptibility, DBA/2J mice
show an incidence of 87% at 21 days of age as contrasted with a 20% incidence for the F1 hybrid and a 0'L incidence for the C57BL/6J animals .
Audiogenic
seizures also depend on the age of the animals at the time of testing.
With
full clonic-tonic seizures as an index the DBA/2J mice are swat susceptible at 21 days of age with an 87% risk .
Seizure incidence is only 13% one week
before and one week after this period .
The same devmlopmental pattern was
obtained for the F1 hybrid whereas C57BL/6J mice never showed the full clonictonic pattern. Table 2 summarizes brain weight, and brain 5-HT and NE levels in these 3 groups of mice at various ages .
Data are presented for total and specific
(per gm wet weight) 5-HT and HE levels .
These data illustrate that the differ
ences in both 5-HT and NE leve1e between the groups are maximal at 21 days of age which corresponds to tho period of maximal seizure susceptibility for the DBA/2J mice .
The differences in total brain 5-HT between DBA/2J and C57BL/6J
mice are approximately 32% at 21 days of age and are statistically significant (t-4 .24 ; df - 12 ; R ,< .01) ; the value for the Fl hybrid is intermediate .
The
differences in total brain NE between DBA/2J and C57BL/6J mice is approximately 44x at 21 days of age and is statistically significant (t - 6 .41 ; df - 12 ; l' <.01) ; the value for the F1 hybrid is intermediate . Brain weights increase slightly from 14 to 42 days of age in all groups . At 21 days of age, however, brain weights of DBA/2J and C57BL/6J mice are not different . Discussion These data agree with those reported by previous investigators in two respects :
first, the importrnce of genetic factors in seizure susceptibility
and second, that the age of the animals at the time of testing is of great importance in seizure susceptibility .
DBAi2J mice were found to be more suscep-
Vol. 4, No . 24
AUDIOGENIC SEIZURES
2348
TABLE 1 Susceptibility to Audiogenic Seizures as a Function of Age
Strain
Age (in days)
if
Seizure Susceptibility
Wild -Running
Clonic
Tonic
27% 87% 40% 40% 7%
13% 87% 13% 7% 0%
DBA/2J DBA/2J DBA/2J DBA/2J DBA/2J
14 21 28 35 42
15 15 15 15 15
73% 100% 87% 67% 27%
C57BL/6J C57BL/6J C57BL/6J C57BL/6J C57BL/6J
14 21 28 35 42
15 15 15 15 15
27% 7% 0% 13% 0%
0% 0% 0% 0% 0% .
0% 0% 0% 0% 0%
B6D2F1 B6D2Fl B6D2F1 B6D2F1 B6D2F1
14 21 28 35 42
15 15 15 15 15
Ox So% 87% 60Z 13x
Ox 20% Ox 13x 0%
20x Ox 7% 0%
tible than C57BL/6J nice and the Fl hybrid was intermediate in susceptibility, although closer to the non-susceptible parent .
The critical period for max-
imum seizure susceptibility, in DBA/2J nice, was quite short (approximately 6 days) ; clonic-tonic seizure incidence was 87% at 21 days of age but only 13% at 14 and 28 days of age . Different investigators have suggested different modes of inheritance for audiogenic seizures ranging from single gene, two gene, to polygenic modes of inheritance (11) .
The results of the present study (Table 1) indicate that
same of the discrepancy may depend on the particular measure used as an index of seizures, i .e ., whether the wild running phase or only full clonic-tonic seizures are used as indices .
Another factor determining the outcome of such
genetic experiments may be the age chosen to measure susceptibility . experiments are in progress to elucidate some of these factors.
Breeding
DBA/2J 7 B6D2Fl 6 C57BL/6J 7
6 DRAW B6D2Fl 7 C57BL/6J 7
DBA/23 6 B6D2Fl 7 C57BL/6J 7
DRAW 6 B6D2F1 6 C57BL/6J 5
21 days
28 days
35 days
42 days " "
"
"
"
"
"
"
DBA/2J 6 36D2Fl 6 C57BL/6J 6
14 days
N
Strain
Age
0 .390 0 .434 0 .421
0 .376 0 .3% 0 .389
0 .418 0 .402 0 .398
0 .328 0 .413 0 .359
0 .340 0 .374 0 .371
±0 .14 +0 .03 +0 .10
±0 .02 ±0 .01 ±0 .01
+0 .27 ±0 .01 ±0 .03
±0 .02 +0 .01 ±0 .21
+0 .15 +0 .01 +0 .17
Brain Weights (8") z s .d .
262 282 255
229 246 231
214 230 235
155 201 228
154 145 185
±33 ±27 +20
+14 +10 ±53
±38 ±15 ±30
±33 + 9 ±10
±25 +18 +19
Total 5H-T (mug) s .d . =
683 652 605
612 622 588
593 574 589
466 485 638
456 388 498
+62 ±74 +46
+43 ±34 ±94
±93 +39 +82
±104 +29 ±28
±88 +46 +54
5-BT Total (2mg/g) x s .d .
212 208 231
163 188 189
152 196 185
105 167 189
121 117 125
+15 +39 +14
±51 +14 ±45
±25 ±23 +55
±31 +17 ±16
±25 +11 +13
Total NE (-s) i s .d .
±73 +47 ±36
±17 +24 +36
555 480 548
+41 ±33 +25
438 ±146 474 ±14 481 ±81
427 +82 489 +60 465 ±144
317 397 526
365 312 337
NE Total (aug/g) x s .d .
Brain Serotonin and Norepinephrine Levels as a Function of Strain and Age
H 0
H
0
Z
AUDIOGENIO SEIZUMS
2350
Vol. 4, No . 24
When genetic and developmental differences in seizure susceptibility were established it was easier to attempt to correlate levels of 5-HT and WE with seizure incidence .
If 5-HT and NE are involved in determining seizure suscep
tibility then we would expect to find differences in levels of these compounds but only at ages at which significant differences in seizure incidence are found .
These data suggest that 5-HT and NE are important in determining sus-
ceptibility to audiogenic seizures since lower levels of these amines in DBA/ 2J mice were found only at the time of maximum seizure risk . The exact role of 5-HT and HE in determining audiogenic seizure susceptibility remains to be explained .
Further, the biochemical mechanism by which
levels of these amines are lowered in DBA/2J mice at 21 days of age is as yet unspecified .
Coleman (5) has suggested that this might be due to the accumul-
ation of abnormal phenylalanine metabolites, a .g ., phenylacetic acid in animals with low phenylalanine hydroxylase activity such as DBA/2J mice .
Phenylacetic
acid has been implicated as an inhibitor of 5-HTP decarboxylase (6) but it is generally accepted that decarbozylation is not the rate-limiting step in the anabolism of 5-HT and NE (12,13) .
Another possible mechanism for the low le-
vels of 5-HT and NE found in DBA/2J mice are the high levels of circulating phenylalanine which might be found in animals with low phenylalanine hydroxylase activity ; McKean, Schanberg and Giarman (14) have shown that high levels of blood phenylalanine inhibit the transport of 5-hydroxytryptophan into brain and that this leads to reduced levels of 5-HT in this organ .
Experiments are
in progress which will attempt to elucidate the mechanism underlying the reduced levels of'15-HT and NE seen in DBA/2J mice at the time of maximal seizure susceptibility . Summary Audiogenic seizure susceptibility was determined in DBA/2J, C57BL/6J, and B6D2F1 mice of various ages .
Audiogenic seizure susceptibility was great-
est in DBA/2J mice which showed an 87% incidence of clonic-tonic seizures at
AUDIOGENIC SEIZUMS
Vol . 4, No . 24
2351
21 days of age ; seizure incidence in this strain was only 13% at 14 and 28 days of age .
B6D2Fl animals staved a lover seizure risk but a similar development-
al pattern.
C57BL/6J mice were resistant to sudiogenic seizures .
Brain levels
of 5-HT and NE were determined in these same groups of mice at the same developmental ages .
Significant differences in 5-HT (32X) and NE (44x) were found
between DBA/2J and C57BL/6J mice ; the values for DBA/2J mice were lower and and the values for the B6D2F1 mice were intermediate .
The differences were
found only at 21 days of age which corresponds to the time of masiul seizure susceptibility in DBA/2J mice . References J. L . FULLER and ELIZABETH WILLIAM, Froc . Nat . Acad . Sci . Wash ., (1951) .
37, 349
2.
DOROTHY S. MILLER, B . E . GIOSBURG and MILDRED A. POTAS, Genetics , 37,605 (1952) .
3.
J. L . FULLER, AU . N. Y . r:cad . Sei., 96, 199 (1962) .
4.
L. G . ABOOD and R. W. GERARD, in Biochemistry of the Developing Nervous System , Academic Press, edit . by H. Waelsch (1955) .
5.
D. L. COLEMAN, Arch . Biochem. Biophy . , 91, 300 (1%0) .
6.
M. SANDLER and H. CLOSE, Lancet , 7098 (II) , 317 (1959) .
7.
A. HANSON, Naturwissenschaften, 45, 423 (1958) .
8.
G. E. JAY, JR., in Methodology in Mammalian Genetics , Holden-Day Inc ., edit . by W . J. Burdette (1963) .
9.
J. L. FULLER, Rec. Genet. Soc . Amer ., 18, 86 (1949) .
10 .
J . MEAD and K. FINGER, Biochem. Pharmacol ., 6, 52 (1%1) .
11 .
J. L. FULLER and W. R . THOMPSON, Behavior Genetics , John W. Wiley and Sons, (1960) .
12 .
T . NAGATSU, M. LEVITT and S . UNDENFRIEND, J. .Biol . Chem . , 239, 2910 (1964) .
13 .
S . SPECTOR, A. SJOERDSMA and S. UDENFRIEND, J. Pharm. Exp . Therap ., 147, 86 (1965) . C . M. MCKEAN, S. M. SCHAMBERG and N. J. GIARMAN, Science, 137, 604 (1%2) .