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Individual differences among mice in normal and amphetamine-enhanced locomotor activity: relationship to behavioral indices of striatal asymmetry
362
Brain Research, 105 (1976) 362-364 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Individual differences among mice in normal and amphetamine-enhanced locomotor activity: relationship to behavioral indices of striatal asymmetry
s. D. GLICK, B. ZIMMERBERG AND S. GREENSTEIN Department of Pharmacology, Mount Sinai School of Medicine o]" the City University of New York, New York, N. Y. 10029 (U.S.A.)
(Accepted December 17th, 1975)
Previous results in this laboratory have indicated that normal rats and mice have an intrinsic asymmetry in nigro-striatal functionl,Z, a. The asymmetry appears to be related to behavioral laterality. Dopamine levels are significantly higher, by 10-15 ~o, in the striatum contralateral vs. the striatum ipsilateral to spontaneous side preferences determined in a T-maze 8. Amphetamine, which increases the asymmetry in dopamine content, induces circling behavior or rotation 4,5 contralateral to the striatum with more dopamine. There is much evidence that the dopaminergic nigrostriatal system, considered bilaterally as a whole, is also involved in the mediation of non-spatial behaviors. For example, normal as well as amphetamine-enhanced locomotor activity may be related to the release of striatal dopamineT; there are no data, however, which indicate whether locomotor activity varies with changes in the degree of asymmetry of the striatal function. This latter problem was approached, albeit indirectly, in the present study. An attempt was made to determine whether there is any relationship between activity and behavioral indices (i.e., spontaneous side preferences and amphetamine-induced rotation) of striatal asymmetry. The subjects were 40 naive female CF1 mice weighing approximately 20 g. Each mouse received two behavioral tests, two weeks apart. One group of 24 mice was tested for side preferences and locomotor activity, and a second group of 16 mice was tested for amphetamine-induced rotation and locomotor activity following amphetamine; the testing order was reversed for half the mice in each group. Side preferences (i.e., an unequal number of left and right choices) were determined in a T-maze constructed of black Plexiglas and a stainless steel grid floor. Mice were placed individually in the long arm of the T-maze with scrambled foot shock (0.3 mA a.c.) administered through the grid floor. The shock was terminated when a mouse entered the left or right arm of the T-maze; the mouse was then removed from the maze. Testing consisted of 10 consecutive trials with 5-15 sec between trials. In preliminary studies, mice as well as rats ~,8 were found to exhibit stable side preferences over daily, weekly and monthly intervals. For measuring rotation (circling behavior), mice were placed individually in a completely automated rotometer 4 which differentiates between complete 360 ° rota-
363 TABLE I CORRELATION OF SPONTANEOUS SIDE PREFERENCES WITH NORMAL LOCOMOTOR ACTIVITY (GROUP 1), AND AMPHETAMINE-INDUCED ROTATION WITH AMPHETAMINE-ENHANCED LOCOMOTOR ACTIVITY (GROUP 2)
Means -t- S.D.
Group 1 Group 2
Side pref (%)
Net rotation
Activity
74.6 -I- 17.2 --
-114.9 -5- 43.7
2347 4- 339 3372 ± 472
Regression coefficient (r)
---0.57* ---0.64*
* Signification correlation at P < 0.01, t-test.
tions and incomplete oscillatory turns. Each mouse was administered D-amphetamine sulfate (5.0 mg/kg, i.p.) 15 min before being tested in the apparatus for 30 min. Rotations to the left and right were recorded on Sodeco counters and the net rotational difference (i.e., rotations in the dominant direction minus rotations in the opposite direction) was determined for each mouse. Previous work has established that net rotation is consistent and positively correlated in magnitude from week to week2,K For measuring locomotor activity, mice were placed individually in Lehigh Valley photocell activity cages (no. 145-03) for 30 min. Responses (photocell counts) were recorded on Sodeco counters. In the mice treated with D-amphetamine sulfate (5.0 mg/kg, i.p.), testing began 15 min after injection. Like side preferences and rotation, normal as well as amphetamine-enhanced locomotor activity is consistent and positively correlated from week to week3, 6. The results are shown in Table I. There were significant inverse correlations between strength of side preferences and locomotor activity and between net rotations and locomotor activity. More active mice, both normally and after D-amphetamine, had lower indices of behavioral laterality than less active mice. To the extent that side preferences s and rotation 1 are manifestations of striatal asymmetry, the present results suggest that individual differences in locomotor activity may be attributable to different degrees of striatal asymmetry. Effects on striatal asymmetry can not account, however, for overall group changes in activity following drug treatment. Thus, for all mice, D-amphetamine both increases locomotor activity and induces rotation, even though the increase in locomotor activity is less in those mice that rotate more. While amphetamine-induced rotation is correlated with an increase in the striatal dopamine asymmetry 1, amphetamine-enhancement of activity is probably related to release of dopamine p e r se in both striata 7. Individual differences in sensitivity to the activity stimulant effect of D-amphetamine depend upon individual differences in baseline activityL Degree of striatal asymmetry may be a primary determinant of such individuality. This research was supported by N I M H Grant MH25644 and N I D A Research Scientist Development Award (Type 2) DA70082 to S. D. Glick.
364 1 GLICK, S. D., JERUSSI, T. P., WATERS,D. H., AND GREEN, J. P., Ampetamine-induced changes in striatal dopamine and acetylcholine levels and relationship to rotation (circling behavior) in rats, Biochem. Pharmacol., 23 (1974) 3223-3225. 2 GLICK, S. D., JEROSSI,T. P., AND ZIMMERBERG,B., Behavioral and neuropharmacological correlates of nigro-striatal asymmetry in rats. In S. HARNAD (Ed.), Lateralization in the Nervous System, Academic Press, New York, in press. 3 GLICK, S. D., AND MILLOY, S., Rate-dependent effects of D-amphetamine on locomotor activity in mice: possible relationship to paradoxical amphetamine sedation in minimal brain dysfunction, Europ. J. PharmacoL, 24 (1973) 266-268. 4 GREENSTEIN,S., AND GLICK, S. D., Improved automated apparatus for recording rotation (circling behavior) in rats or mice, Pharm. Biochem. Behav., 3 (1975) 507-510. 5 JERUSSl,T. P., AND GLICK, S. D., Amphetamine-induced rotation in rats without lesions, Neuropharmacology, 13 (1974) 283-286. 6 MILLOY,S., AND GLICK, S. D., unpublished results, 7 THORNBURG,J. E., AND MOORE,K. E., The relative importance of dopaminergic and noradrenergic n~uronal systems for the stimulation of locomotor activity induced by amphetamine and other drugs, Neuropharmacology, 12 (1973) 853-866. 8 ZrMMERaERG,B., GLICK, S. D., AND JERUSSI,T. P., Neurochemical correlate of a spatial preference in rats, Science, 185 (1974) 623-625.
Brain Research, 105 (1976) 362-364 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Individual differences among mice in normal and amphetamine-enhanced locomotor activity: relationship to behavioral indices of striatal asymmetry
s. D. GLICK, B. ZIMMERBERG AND S. GREENSTEIN Department of Pharmacology, Mount Sinai School of Medicine o]" the City University of New York, New York, N. Y. 10029 (U.S.A.)
(Accepted December 17th, 1975)
Previous results in this laboratory have indicated that normal rats and mice have an intrinsic asymmetry in nigro-striatal functionl,Z, a. The asymmetry appears to be related to behavioral laterality. Dopamine levels are significantly higher, by 10-15 ~o, in the striatum contralateral vs. the striatum ipsilateral to spontaneous side preferences determined in a T-maze 8. Amphetamine, which increases the asymmetry in dopamine content, induces circling behavior or rotation 4,5 contralateral to the striatum with more dopamine. There is much evidence that the dopaminergic nigrostriatal system, considered bilaterally as a whole, is also involved in the mediation of non-spatial behaviors. For example, normal as well as amphetamine-enhanced locomotor activity may be related to the release of striatal dopamineT; there are no data, however, which indicate whether locomotor activity varies with changes in the degree of asymmetry of the striatal function. This latter problem was approached, albeit indirectly, in the present study. An attempt was made to determine whether there is any relationship between activity and behavioral indices (i.e., spontaneous side preferences and amphetamine-induced rotation) of striatal asymmetry. The subjects were 40 naive female CF1 mice weighing approximately 20 g. Each mouse received two behavioral tests, two weeks apart. One group of 24 mice was tested for side preferences and locomotor activity, and a second group of 16 mice was tested for amphetamine-induced rotation and locomotor activity following amphetamine; the testing order was reversed for half the mice in each group. Side preferences (i.e., an unequal number of left and right choices) were determined in a T-maze constructed of black Plexiglas and a stainless steel grid floor. Mice were placed individually in the long arm of the T-maze with scrambled foot shock (0.3 mA a.c.) administered through the grid floor. The shock was terminated when a mouse entered the left or right arm of the T-maze; the mouse was then removed from the maze. Testing consisted of 10 consecutive trials with 5-15 sec between trials. In preliminary studies, mice as well as rats ~,8 were found to exhibit stable side preferences over daily, weekly and monthly intervals. For measuring rotation (circling behavior), mice were placed individually in a completely automated rotometer 4 which differentiates between complete 360 ° rota-
363 TABLE I CORRELATION OF SPONTANEOUS SIDE PREFERENCES WITH NORMAL LOCOMOTOR ACTIVITY (GROUP 1), AND AMPHETAMINE-INDUCED ROTATION WITH AMPHETAMINE-ENHANCED LOCOMOTOR ACTIVITY (GROUP 2)
Means -t- S.D.
Group 1 Group 2
Side pref (%)
Net rotation
Activity
74.6 -I- 17.2 --
-114.9 -5- 43.7
2347 4- 339 3372 ± 472
Regression coefficient (r)
---0.57* ---0.64*
* Signification correlation at P < 0.01, t-test.
tions and incomplete oscillatory turns. Each mouse was administered D-amphetamine sulfate (5.0 mg/kg, i.p.) 15 min before being tested in the apparatus for 30 min. Rotations to the left and right were recorded on Sodeco counters and the net rotational difference (i.e., rotations in the dominant direction minus rotations in the opposite direction) was determined for each mouse. Previous work has established that net rotation is consistent and positively correlated in magnitude from week to week2,K For measuring locomotor activity, mice were placed individually in Lehigh Valley photocell activity cages (no. 145-03) for 30 min. Responses (photocell counts) were recorded on Sodeco counters. In the mice treated with D-amphetamine sulfate (5.0 mg/kg, i.p.), testing began 15 min after injection. Like side preferences and rotation, normal as well as amphetamine-enhanced locomotor activity is consistent and positively correlated from week to week3, 6. The results are shown in Table I. There were significant inverse correlations between strength of side preferences and locomotor activity and between net rotations and locomotor activity. More active mice, both normally and after D-amphetamine, had lower indices of behavioral laterality than less active mice. To the extent that side preferences s and rotation 1 are manifestations of striatal asymmetry, the present results suggest that individual differences in locomotor activity may be attributable to different degrees of striatal asymmetry. Effects on striatal asymmetry can not account, however, for overall group changes in activity following drug treatment. Thus, for all mice, D-amphetamine both increases locomotor activity and induces rotation, even though the increase in locomotor activity is less in those mice that rotate more. While amphetamine-induced rotation is correlated with an increase in the striatal dopamine asymmetry 1, amphetamine-enhancement of activity is probably related to release of dopamine p e r se in both striata 7. Individual differences in sensitivity to the activity stimulant effect of D-amphetamine depend upon individual differences in baseline activityL Degree of striatal asymmetry may be a primary determinant of such individuality. This research was supported by N I M H Grant MH25644 and N I D A Research Scientist Development Award (Type 2) DA70082 to S. D. Glick.
364 1 GLICK, S. D., JERUSSI, T. P., WATERS,D. H., AND GREEN, J. P., Ampetamine-induced changes in striatal dopamine and acetylcholine levels and relationship to rotation (circling behavior) in rats, Biochem. Pharmacol., 23 (1974) 3223-3225. 2 GLICK, S. D., JEROSSI,T. P., AND ZIMMERBERG,B., Behavioral and neuropharmacological correlates of nigro-striatal asymmetry in rats. In S. HARNAD (Ed.), Lateralization in the Nervous System, Academic Press, New York, in press. 3 GLICK, S. D., AND MILLOY, S., Rate-dependent effects of D-amphetamine on locomotor activity in mice: possible relationship to paradoxical amphetamine sedation in minimal brain dysfunction, Europ. J. PharmacoL, 24 (1973) 266-268. 4 GREENSTEIN,S., AND GLICK, S. D., Improved automated apparatus for recording rotation (circling behavior) in rats or mice, Pharm. Biochem. Behav., 3 (1975) 507-510. 5 JERUSSl,T. P., AND GLICK, S. D., Amphetamine-induced rotation in rats without lesions, Neuropharmacology, 13 (1974) 283-286. 6 MILLOY,S., AND GLICK, S. D., unpublished results, 7 THORNBURG,J. E., AND MOORE,K. E., The relative importance of dopaminergic and noradrenergic n~uronal systems for the stimulation of locomotor activity induced by amphetamine and other drugs, Neuropharmacology, 12 (1973) 853-866. 8 ZrMMERaERG,B., GLICK, S. D., AND JERUSSI,T. P., Neurochemical correlate of a spatial preference in rats, Science, 185 (1974) 623-625.