- Email: [email protected]
Heritable differences in turning behavior of rats
Life Sciences, Vol. 36, pp. 499-503 Printed in the U.S.A.
Pergamon Press
HERITABLE DIFFERENCES IN TURNING BEHAVIOR OF RATS Stanley D. Glick Department of Pharmacology, Mount Sinai School of Medicine C i t y U n i v e r s i t y of New York, One Gustave L. Levy Place New York, N.Y. 10029 Present address: Department of Pharmacology and Toxicology Albany Medical College, Albany, N.Y. 12208 (Received in final form November 19, 1984)
Summary An a t t e m p t was made t o breed s t r a i n s o f s t r o n g l y and w e a k l y r o t a t i n g rats. A s t r a i n d i f f e r e n c e in r o t a t i o n parameters was limited t o f e m a l e s and d e v e l o p e d g r a d u a l l y o v e r e i g h t generations before asymptoting. Unexpectedly, a left-sided population bias developed in both male and female rats bred f o r weak r o t a t i o n . I t i s suggested t h a t t e s t o s t e r o n e modulates several aspects of the i n h e r i t a n c e of cerebral l a t e r a l i z a t i o n . Research conducted in t h i s l a b o r a t o r y and o t h e r s has e s t a b l i s h e d t h a t normal r a t s t u r n i n c i r c l e s at n i g h t and in response to d o p a m i n e r g i c drugs during the daytime. C i r c l i n g i s a m a n i f e s t a t i o n of a p e r s i s t e n t and consistent left or r i g h t s i d e p r e f e r e n c e and appears to r e s u l t from l a t e r a l i z e d f u n c t i o n i n g of the dopaminergic n i g r o s t r i a t a l pathways in brain (1,2) . Side and t u r n i n g p r e f e r e n c e s o f r a t s have been shown t o be r e l a t e d t o endogenous asymmetries in s t r i a t a l dopamine content, metabolism and receptor a c t i v i t y . The i n t e n s i t y of c i r c l i n g behavior as well as the r e l a t i v e incidence of l e f t and right-sidedness v a r i e s among s t r a i n s (3,4) as well as between sexes (5,6). Previous work has suggested t h a t whether a p a r t i c u l a r r a t develops a l e f t or r i g h t preference is complexly determined by an i n t e r a c t i o n between h e r i t a b l e and s e x - r e l a t e d hormonal v a r i a b l e s (7). The present study i n d i c a t e s t h a t the s t r e n g t h o f l e f t or r i g h t p r e f e r e n c e s i s a l s o , in p a r t , under h e r i t a b l e and s e x u a l l y modulated c o n t r o l . M a t e r i a l s and Methods The o b j e c t i v e was to breed s t r a i n s of s t r o n g l y and weakly l a t e r a l i z e d r a t s - - i . e . , one s t r a i n e x h i b i t i n g i n t e n s e c i r c l i n g b e h a v i o r in a p r e f e r r e d d i r e c t i o n and another s t r a i n e x h i b i t i n g l i t t l e or no d i r e c t i o n a l preference in c i r c l i n g behavior. Adult (80-100 days of age) male and female Sprague-Dawley r a t s , o r i g i n a l l y obtained from Perfection Breeders ( D o u g l a s s v i l l e , PA), were placed i n d i v i d u a l l y in an automated apparatus (8) in which c i r c l i n g behavior (or r o t a t i o n ) was measured f o r 24 hours (12 l i g h t , 12 dark; cf. 9). Rats were i d e n t i f i e d as e i t h e r l e f t or r i g h t r o t a t o r s or non-rotators in accordance with established procedures (3). A l l rats were also tested i n d i v i d u a l l y in photoc e l l a c t i v i t y boxes (I0) f o r 30 minutes on the day a f t e r r o t a t i o n t e s t i n g . To be used f o r breeding the s t r o n g l y l a t e r a l i z e d (SL) s t r a i n , rats were required t o make at l e a s t 60 net r o t a t i o n s (360 o t u r n s in p r e f e r r e d d i r e c t i o n minus
0024-3205/85 $3.00 + .00 Copyright (c) 1985 Pergamon Press Ltd.
500
Heritable Differences
in Turning Behavior
Vol. 36, No. 5, 1985
those in non-preferred direction) per 24 hours with at least 85% of the total r o t a t i o n s being in a preferred d i r e c t i o n (% preference= 100 x r o t a t i o n s in preferred d i r e c t i o n divided by t o t a l r o t a t i o n s ) . O n l y rats making f i v e or less net r o t a t i o n s per 24 hours and having no more than 55% of the t o t a l rotations in a preferred direction were used for breeding the weakly l a t e r a l ized (WL) strain. Matings for the SL strain were arranged such that a l l four possible combinations of directional phenotypes (i.e., l e f t female with right male, l e f t female with l e f t male etc.) would be equally represented. Female rats were housed in large breeding cages during mating (one week) and gestation and f o r the f i r s t 21 days a f t e r d e l i v e r y . Pups were then weaned, and the sexes were separated and housed in standard group cages until testing as adults. All rats were then subjected to rotation and a c t i v i t y testing as conducted i n i t i a l l y and new matings chosen on the basis of the o r i g i n a l c r i t e r i a . All matings of the f i r s t four generations were b r o t h e r - s i s t e r . Thereafter, for the next eight generations, outbreeding was alternated with brother-sister mating in order to prevent the establishment of substrains and maintain the maximum variation of extreme phenotypes (e.g., 11). Results Table I shows that a s t r a i n d i f f e r e n c e in r o t a t i o n parameters was l i m i t e d to females and developed g r a d ual l y over e i g h t generations before asymptoting. TABLE I Development of sex-dependent s t r a i n d i f f erences in r o t a t i o n a l behavior: mean net rotations (Net) and % preference (%P) of WL and SL rats WL
SL
Male Net %P N
Female Net %P N
Male Net %P N
Female Net %P N
I
30
66
9
39
69
9
32
66
11
38
69
8
2
25
66
10
36
69
13
28
66
11
40
68
10
3
25
66
9
38
68
12
29
66
9
39
69
9
4
26
65
21
34
67
25
25
66
11
44
70
16
5
24
66
26
34
67
18
26
67
12
47
70
17
6
31
67
22
35
67
16
30
67
11
56
73
13
7
32
66
28
36
68
30
28
67
21
66
72
19
8
31
66
30
34
66
28
33
66
22
70
74
26
9
33
65
28
32
65
28
38
67
23
73
75
21
10
30
67
24
34
66
30
31
66
22
71
73
19
11
33
66
29
33
66
20
33
66
18
74
74
20
12
31
66
24
33
66
31
33
67
18
72
74
20
Generation
Vol. 36, No. 5, 1985
Heritable Differences in Turnin~ Behavior
501
The data from the eighth through the t w e l f t h generations were combined for further analysis (Table I I ) . The weaker rotation of females in the WL strain resulted in the disappearance of a sex difference normally present in randombred animals ( l e f t - and right-sided rats combined, p
Male (81)
Rotation* Net Rotations % Preference
Activity Photocell Counts
30.7+5.1
66.1+1.3
1478.8+42.4
Right Male ( 5 4 )
33.3+7.1
65.8+1.6
1562.6+52.1
Left Female ( 8 0 )
31.5+5.1
65.8+1.3
1845.7+54.0
Right Female ( 5 7 )
35.6+6.8
65.8+1.3
1924.5+59.8
SL Left Male (51)
31.7+6.5
66.4+1.7
1548.0+48.6
Right Male ( 5 2 )
35.7+6.2
66.4+1.6
1587.1+44.3
Left Female ( 4 7 )
70.1+11.1
73.1+1.7
1806.4+59.1
Right Female ( 5 9 )
73.4+10.9
74.7+1.6
1844.0+68.9
Random-Bred el/e-f-t Male ~49)
30.6+4.9
65.9+1.8
1522.3+50.1
Right Male ( 4 8 )
34.6+5.0
66.0+1.9
1538.8+52.5
Left Female ( 4 8 )
38.9+6.3
66.6+1.8
1778.9+44.8
Right Female ( 5 5 )
46.6+7.2
70.3+1.5
1892.1+47.7
*Significant interaction between group and sex in two-way analysis of variance for each measure (p<0.02-0.01) and significant differences in both measures between respective WL and SL female groups (p<0.005-0.001, t-tests).
502
Heritable Differences in Turning Behavior
Vol. 36, No. 5, 1985
Discussion The results of this study indicate that the strength of side preferences is separable from the l e v e l of locomotor a c t i v i t y and to some extent h e r i t a b l e . However, the complexity of the results with respect to sexdependence argues against any simple pattern of inheritance. I n t e r a c t i v e e f f e c t s of hormones on gene expression may be i m p o r t a n t l y i n v o l v e d - p a r t i cu l a r l y the effects of testosterone exposure, in utero and/or soon after p a r t u r i t i o n . Testosterone has been postulated to modulate at least three aspects of the inheritance of cerebral l a t e r a l i z a t i o n : (i) The extent to which l e f t - r i g h t biases of female offspring resemble those of the female parent varies with the sex r a t i o of a l i t t e r (7). Based on reports i n d i c a t i n g a p o s i t i v e r e l a t i o n s h i p between the sex r a t i o (male/female) of a l i t t e r and levels of testosterone in female fetuses, i t was previously suggested (7) that in utero exposure to testosterone reverses the coding of a h e r i t a b l e female i n fl u e nce and induces a tendency f o r the offspring to have l e f t - r i g h t biases that are opposite in direction to those of the female parent. ( i i ) Neonatal or p e r i n a t a l exposure to testosterone may masculinize the central nervous system (12) and, by inducing female rats to exhibit malel i k e behavior patterns (e.g., 13,14), reduce adult sex d i f f e r e n c e s . Hence, the normal adult sex d i f f e r e n c e in rates of r o t a t i o n is greatest in l i t t e r s having more females than males and smallest in l i t t e r s having more males than Females ( 7 ) . Predictably, neonatal administration of testoterone propionate (1.25 mg, s.c.) w i l l reduce adult r o t a t i o n in female rats (Brass and Glick, unpublished results). In the present study, the distribution of l i t t e r s with respect to sex r a t i o was similar in the WL, SL and random-bred animals so that d i f f e r e n t i a l exposure to testosterone cannot l i k e l y account f o r the s t r a i n differences in rates of female rotation. However, the absence of a breeding e f f e c t on the rates of male r o t a t i o n might be a t t r i b u t a b l e to a dampening e f f e c t of the obviously stronger and longer (i.e., postnatal) exposure to testosterone in males. ( i i i ) Testosterone has been hypothesized to delay p r e f e r e n t i a l l y the development of c e r t a i n structures in the l e f t side of the brain (15) and, as one r e s u l t in humans, to be responsible f o r the greater incidence of l e f t handedness in males versus females. The l e f t bias in the WL strain may have developed, perhaps, because the parents were selected for having very weak or n e g l i g i b l e l e f t - r i g h t preferences and the e f f e c t of testosterone on brain maturation could be exerted independently of a parental directional influence (7). Further studies w i l l h o p e f u l l y enhance our understanding of the mechanisms mediating these s t r a i n e f f e c t s . Behavioral, anatomical and neurochemical characterization of SL and WL animals should reveal fundamental properties of brain l a t e r a l i z a t i o n that are amenable to s e l e c t i v e pressures and ultimately lead to animal models of phenomena exhibited by humans (cf.
16).
Vol. 36, No. 5, 1985
Heritable Differences
in Turning Behavior
503
Acknowledgements Supported by grants NS 14812 and DA 01044. I wish to thank Russell Cox, Ronald Guido and Patricia Hinds for technical assistance. References I. 2. 3. 4. 5. 6. 7. 8. 9. 10. II. 12. 13. 14. 15. 16.
S.D. GLICK, T.P. JERUSSI, and B. ZIMMERBERG., L a t e r a l i z a t i o n in the Nervous System , S. Harnad, R.W. Dory, L. Goldstein, J. Jaynes, ~nd G. Krauthamer (Eds.), p. 213, Academic Press, New York (1977). S.D. GLICK, Hemisyndromes: Psychobiology, Neurology, Psychiatry, M.S. Myslobodsky, (Ed.), p. 7, Academic Press, New York (1983). S.D. GLICK and D.A. ROSS, Brain Res. 205, 222 (1981). V.H. DENENBERG, Behav. Brain Sci. 4, I (1981). C.A. BRASS and S.D. GLICK, Brain ~ s . 223, 229 (1981). T.E. ROBINSON, J.B. BECKER, and V.D. RAMIREZ, Brain Res. Bull. 5, 539 (1980). S.D. GLICK, Life Sci. 3__2, 2215 (1983). S. GREENSTEIN and S.0. GLICK, Pharmacol. Biochem. Behav. ~, 507 (1975). S.D. GLICK and R.D. COX, Brain Res. 150, 149 (1978). S.D. GLICK, Europ. J. Pharmacol. 2__~0,~I (1972). K. ERIKSSON, Ann. N.Y. Acad. Sci. 197, 32 (1972). N.J. MACLUSKYand F. NAFTOLIN, Science 211, 1294 (1981). L.G. CLEMENS, B.A. GLADUE, and L.P. CONI--GI]IO, Horm. Res. I0, 40 (1978). R.L. MEISEL and I.L. WARD, Science 213, 239 (1981). N. GESCHWINDand B. BEHAN, Proc. NatT. Acad. Sci. USA 79, 5097 (1982). N. GESCHWIND, Cerebral L a t e r a l i z a t i o n in Nonhuman Species, S. D. Glick (Ed.), Academic Press, New York, in press.
Pergamon Press
HERITABLE DIFFERENCES IN TURNING BEHAVIOR OF RATS Stanley D. Glick Department of Pharmacology, Mount Sinai School of Medicine C i t y U n i v e r s i t y of New York, One Gustave L. Levy Place New York, N.Y. 10029 Present address: Department of Pharmacology and Toxicology Albany Medical College, Albany, N.Y. 12208 (Received in final form November 19, 1984)
Summary An a t t e m p t was made t o breed s t r a i n s o f s t r o n g l y and w e a k l y r o t a t i n g rats. A s t r a i n d i f f e r e n c e in r o t a t i o n parameters was limited t o f e m a l e s and d e v e l o p e d g r a d u a l l y o v e r e i g h t generations before asymptoting. Unexpectedly, a left-sided population bias developed in both male and female rats bred f o r weak r o t a t i o n . I t i s suggested t h a t t e s t o s t e r o n e modulates several aspects of the i n h e r i t a n c e of cerebral l a t e r a l i z a t i o n . Research conducted in t h i s l a b o r a t o r y and o t h e r s has e s t a b l i s h e d t h a t normal r a t s t u r n i n c i r c l e s at n i g h t and in response to d o p a m i n e r g i c drugs during the daytime. C i r c l i n g i s a m a n i f e s t a t i o n of a p e r s i s t e n t and consistent left or r i g h t s i d e p r e f e r e n c e and appears to r e s u l t from l a t e r a l i z e d f u n c t i o n i n g of the dopaminergic n i g r o s t r i a t a l pathways in brain (1,2) . Side and t u r n i n g p r e f e r e n c e s o f r a t s have been shown t o be r e l a t e d t o endogenous asymmetries in s t r i a t a l dopamine content, metabolism and receptor a c t i v i t y . The i n t e n s i t y of c i r c l i n g behavior as well as the r e l a t i v e incidence of l e f t and right-sidedness v a r i e s among s t r a i n s (3,4) as well as between sexes (5,6). Previous work has suggested t h a t whether a p a r t i c u l a r r a t develops a l e f t or r i g h t preference is complexly determined by an i n t e r a c t i o n between h e r i t a b l e and s e x - r e l a t e d hormonal v a r i a b l e s (7). The present study i n d i c a t e s t h a t the s t r e n g t h o f l e f t or r i g h t p r e f e r e n c e s i s a l s o , in p a r t , under h e r i t a b l e and s e x u a l l y modulated c o n t r o l . M a t e r i a l s and Methods The o b j e c t i v e was to breed s t r a i n s of s t r o n g l y and weakly l a t e r a l i z e d r a t s - - i . e . , one s t r a i n e x h i b i t i n g i n t e n s e c i r c l i n g b e h a v i o r in a p r e f e r r e d d i r e c t i o n and another s t r a i n e x h i b i t i n g l i t t l e or no d i r e c t i o n a l preference in c i r c l i n g behavior. Adult (80-100 days of age) male and female Sprague-Dawley r a t s , o r i g i n a l l y obtained from Perfection Breeders ( D o u g l a s s v i l l e , PA), were placed i n d i v i d u a l l y in an automated apparatus (8) in which c i r c l i n g behavior (or r o t a t i o n ) was measured f o r 24 hours (12 l i g h t , 12 dark; cf. 9). Rats were i d e n t i f i e d as e i t h e r l e f t or r i g h t r o t a t o r s or non-rotators in accordance with established procedures (3). A l l rats were also tested i n d i v i d u a l l y in photoc e l l a c t i v i t y boxes (I0) f o r 30 minutes on the day a f t e r r o t a t i o n t e s t i n g . To be used f o r breeding the s t r o n g l y l a t e r a l i z e d (SL) s t r a i n , rats were required t o make at l e a s t 60 net r o t a t i o n s (360 o t u r n s in p r e f e r r e d d i r e c t i o n minus
0024-3205/85 $3.00 + .00 Copyright (c) 1985 Pergamon Press Ltd.
500
Heritable Differences
in Turning Behavior
Vol. 36, No. 5, 1985
those in non-preferred direction) per 24 hours with at least 85% of the total r o t a t i o n s being in a preferred d i r e c t i o n (% preference= 100 x r o t a t i o n s in preferred d i r e c t i o n divided by t o t a l r o t a t i o n s ) . O n l y rats making f i v e or less net r o t a t i o n s per 24 hours and having no more than 55% of the t o t a l rotations in a preferred direction were used for breeding the weakly l a t e r a l ized (WL) strain. Matings for the SL strain were arranged such that a l l four possible combinations of directional phenotypes (i.e., l e f t female with right male, l e f t female with l e f t male etc.) would be equally represented. Female rats were housed in large breeding cages during mating (one week) and gestation and f o r the f i r s t 21 days a f t e r d e l i v e r y . Pups were then weaned, and the sexes were separated and housed in standard group cages until testing as adults. All rats were then subjected to rotation and a c t i v i t y testing as conducted i n i t i a l l y and new matings chosen on the basis of the o r i g i n a l c r i t e r i a . All matings of the f i r s t four generations were b r o t h e r - s i s t e r . Thereafter, for the next eight generations, outbreeding was alternated with brother-sister mating in order to prevent the establishment of substrains and maintain the maximum variation of extreme phenotypes (e.g., 11). Results Table I shows that a s t r a i n d i f f e r e n c e in r o t a t i o n parameters was l i m i t e d to females and developed g r a d ual l y over e i g h t generations before asymptoting. TABLE I Development of sex-dependent s t r a i n d i f f erences in r o t a t i o n a l behavior: mean net rotations (Net) and % preference (%P) of WL and SL rats WL
SL
Male Net %P N
Female Net %P N
Male Net %P N
Female Net %P N
I
30
66
9
39
69
9
32
66
11
38
69
8
2
25
66
10
36
69
13
28
66
11
40
68
10
3
25
66
9
38
68
12
29
66
9
39
69
9
4
26
65
21
34
67
25
25
66
11
44
70
16
5
24
66
26
34
67
18
26
67
12
47
70
17
6
31
67
22
35
67
16
30
67
11
56
73
13
7
32
66
28
36
68
30
28
67
21
66
72
19
8
31
66
30
34
66
28
33
66
22
70
74
26
9
33
65
28
32
65
28
38
67
23
73
75
21
10
30
67
24
34
66
30
31
66
22
71
73
19
11
33
66
29
33
66
20
33
66
18
74
74
20
12
31
66
24
33
66
31
33
67
18
72
74
20
Generation
Vol. 36, No. 5, 1985
Heritable Differences in Turnin~ Behavior
501
The data from the eighth through the t w e l f t h generations were combined for further analysis (Table I I ) . The weaker rotation of females in the WL strain resulted in the disappearance of a sex difference normally present in randombred animals ( l e f t - and right-sided rats combined, p
Male (81)
Rotation* Net Rotations % Preference
Activity Photocell Counts
30.7+5.1
66.1+1.3
1478.8+42.4
Right Male ( 5 4 )
33.3+7.1
65.8+1.6
1562.6+52.1
Left Female ( 8 0 )
31.5+5.1
65.8+1.3
1845.7+54.0
Right Female ( 5 7 )
35.6+6.8
65.8+1.3
1924.5+59.8
SL Left Male (51)
31.7+6.5
66.4+1.7
1548.0+48.6
Right Male ( 5 2 )
35.7+6.2
66.4+1.6
1587.1+44.3
Left Female ( 4 7 )
70.1+11.1
73.1+1.7
1806.4+59.1
Right Female ( 5 9 )
73.4+10.9
74.7+1.6
1844.0+68.9
Random-Bred el/e-f-t Male ~49)
30.6+4.9
65.9+1.8
1522.3+50.1
Right Male ( 4 8 )
34.6+5.0
66.0+1.9
1538.8+52.5
Left Female ( 4 8 )
38.9+6.3
66.6+1.8
1778.9+44.8
Right Female ( 5 5 )
46.6+7.2
70.3+1.5
1892.1+47.7
*Significant interaction between group and sex in two-way analysis of variance for each measure (p<0.02-0.01) and significant differences in both measures between respective WL and SL female groups (p<0.005-0.001, t-tests).
502
Heritable Differences in Turning Behavior
Vol. 36, No. 5, 1985
Discussion The results of this study indicate that the strength of side preferences is separable from the l e v e l of locomotor a c t i v i t y and to some extent h e r i t a b l e . However, the complexity of the results with respect to sexdependence argues against any simple pattern of inheritance. I n t e r a c t i v e e f f e c t s of hormones on gene expression may be i m p o r t a n t l y i n v o l v e d - p a r t i cu l a r l y the effects of testosterone exposure, in utero and/or soon after p a r t u r i t i o n . Testosterone has been postulated to modulate at least three aspects of the inheritance of cerebral l a t e r a l i z a t i o n : (i) The extent to which l e f t - r i g h t biases of female offspring resemble those of the female parent varies with the sex r a t i o of a l i t t e r (7). Based on reports i n d i c a t i n g a p o s i t i v e r e l a t i o n s h i p between the sex r a t i o (male/female) of a l i t t e r and levels of testosterone in female fetuses, i t was previously suggested (7) that in utero exposure to testosterone reverses the coding of a h e r i t a b l e female i n fl u e nce and induces a tendency f o r the offspring to have l e f t - r i g h t biases that are opposite in direction to those of the female parent. ( i i ) Neonatal or p e r i n a t a l exposure to testosterone may masculinize the central nervous system (12) and, by inducing female rats to exhibit malel i k e behavior patterns (e.g., 13,14), reduce adult sex d i f f e r e n c e s . Hence, the normal adult sex d i f f e r e n c e in rates of r o t a t i o n is greatest in l i t t e r s having more females than males and smallest in l i t t e r s having more males than Females ( 7 ) . Predictably, neonatal administration of testoterone propionate (1.25 mg, s.c.) w i l l reduce adult r o t a t i o n in female rats (Brass and Glick, unpublished results). In the present study, the distribution of l i t t e r s with respect to sex r a t i o was similar in the WL, SL and random-bred animals so that d i f f e r e n t i a l exposure to testosterone cannot l i k e l y account f o r the s t r a i n differences in rates of female rotation. However, the absence of a breeding e f f e c t on the rates of male r o t a t i o n might be a t t r i b u t a b l e to a dampening e f f e c t of the obviously stronger and longer (i.e., postnatal) exposure to testosterone in males. ( i i i ) Testosterone has been hypothesized to delay p r e f e r e n t i a l l y the development of c e r t a i n structures in the l e f t side of the brain (15) and, as one r e s u l t in humans, to be responsible f o r the greater incidence of l e f t handedness in males versus females. The l e f t bias in the WL strain may have developed, perhaps, because the parents were selected for having very weak or n e g l i g i b l e l e f t - r i g h t preferences and the e f f e c t of testosterone on brain maturation could be exerted independently of a parental directional influence (7). Further studies w i l l h o p e f u l l y enhance our understanding of the mechanisms mediating these s t r a i n e f f e c t s . Behavioral, anatomical and neurochemical characterization of SL and WL animals should reveal fundamental properties of brain l a t e r a l i z a t i o n that are amenable to s e l e c t i v e pressures and ultimately lead to animal models of phenomena exhibited by humans (cf.
16).
Vol. 36, No. 5, 1985
Heritable Differences
in Turning Behavior
503
Acknowledgements Supported by grants NS 14812 and DA 01044. I wish to thank Russell Cox, Ronald Guido and Patricia Hinds for technical assistance. References I. 2. 3. 4. 5. 6. 7. 8. 9. 10. II. 12. 13. 14. 15. 16.
S.D. GLICK, T.P. JERUSSI, and B. ZIMMERBERG., L a t e r a l i z a t i o n in the Nervous System , S. Harnad, R.W. Dory, L. Goldstein, J. Jaynes, ~nd G. Krauthamer (Eds.), p. 213, Academic Press, New York (1977). S.D. GLICK, Hemisyndromes: Psychobiology, Neurology, Psychiatry, M.S. Myslobodsky, (Ed.), p. 7, Academic Press, New York (1983). S.D. GLICK and D.A. ROSS, Brain Res. 205, 222 (1981). V.H. DENENBERG, Behav. Brain Sci. 4, I (1981). C.A. BRASS and S.D. GLICK, Brain ~ s . 223, 229 (1981). T.E. ROBINSON, J.B. BECKER, and V.D. RAMIREZ, Brain Res. Bull. 5, 539 (1980). S.D. GLICK, Life Sci. 3__2, 2215 (1983). S. GREENSTEIN and S.0. GLICK, Pharmacol. Biochem. Behav. ~, 507 (1975). S.D. GLICK and R.D. COX, Brain Res. 150, 149 (1978). S.D. GLICK, Europ. J. Pharmacol. 2__~0,~I (1972). K. ERIKSSON, Ann. N.Y. Acad. Sci. 197, 32 (1972). N.J. MACLUSKYand F. NAFTOLIN, Science 211, 1294 (1981). L.G. CLEMENS, B.A. GLADUE, and L.P. CONI--GI]IO, Horm. Res. I0, 40 (1978). R.L. MEISEL and I.L. WARD, Science 213, 239 (1981). N. GESCHWINDand B. BEHAN, Proc. NatT. Acad. Sci. USA 79, 5097 (1982). N. GESCHWIND, Cerebral L a t e r a l i z a t i o n in Nonhuman Species, S. D. Glick (Ed.), Academic Press, New York, in press.