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Lateralizing effects of apomorphine on taxis, postural support and rotation in rats
Pmg. Neuro-Psychopharmacol. 6 Bid. Psychiat. 1985. Vol. 9. pp. 525-531 Printed in Great Britain All rights reserved.
LATERALIZING
027&5846/85 $0.00 + .50 Copyright @ 1985 Pergamon Press Ltd.
EFFECTS OF APOMORPHINE ON TAXIS, POSTURAL SUPPORT AND ROTATION IN RATS
MICHEIEPISAl'*and HENRY SZECHWIAN1 and 2Psychiatry %a partientof Neurosciences McMasterUniversity, Hamilton,Ontario,Canada (Finalform, July 1985) Abstract Pisa, Michele and Henry Szechtman:Lateralizing effectsof apcxnorphine on taxis,postural supportand rotationin rats. Prog. Neuro-Psychopharmacol. & Biol. Psychiat.1985,-9 (5/6):525-531. 1. Subcutaneous injections of apunorphine,a dopamine receptor agonist, induced a lateralization of taxis for edges in 16% of rats and a reliablelateralization of posturalsupportin 82% of rats. 2. The relation among these effects and the lateralizingeffects of aptmorphineon rotationalbehaviorwere examined. Lateralizedrotationdid not reliablycorrelate with lateralizedtaxis. HOwever,it correlatedwith a relativelylarge asymmetryof posturalsupport. 3. The lateralizingeffectsof apanorphineon taxisand rotationmay reflectattentional and directionalasymmetries, respectively.It is proposedthat apcmorphinecan induce differenttypes of lateralizations, includingattentional,posturaland directional, and that the lateralizingeffectsof apcmorphineon postureand locanotordirection are interrelated.Regionalbrain interhemispheric asynmetriesin the responsiviness of dopamine receptors may underlie different types of apcmorphine-induced lateralizations. Keywords: apcmorphine, dopamine,lateralization, taxis,posture,rotation,attention. Introduction tqoamincmimetic drugs such as amphetamineor apanorphine can increaselocanotionin rats (Maj et al., 1972; Rardrupet al., 1963). This effect is often attendedby a preference to turn in a specificdirection(Jerussiand Glick, 1976). There is evidencesuggesting that an asymmetricalactivationof striataldopaminergictransmission accountsfor such lateralization of turning (Jerussiand Glick, 1976). The behavioralmechanismof this phencmenonis still controversial, however. The lateralizedturningmight reflecteither a spatiallateralization, namelya preferenceof locanotordirectionunrelatedto specific externalstimuli,or a lateralization of taxis, namely,a preferenceto move in relation to specificstimuli locatedon a specificside of the body, or a posturallateralization, namely,a preferenceto use a specifichindlq for posturalsupportand the other hindleg for stepping,or a ccrnbination of these. There is no direct evidence,however,as to whether or not dopaminanimetic drugs have lateralizing effectson any of thesebehavioral processes. Thus, a study to this effect would be the prerequisite step toward understandingthe functionalbasis of the lateralization of turning. Accordingly,the primary objective of this study was to exmnine whether peripheraladministrationof apanorphine,a dopaminereceptoragonist,can indeed induce lateralizations of taxis and posturalsupport. To examine lateralization of taxis,we proceededfrom the preliminaryobservationthat, after doses of amorphine that elicithyperlocanotion, scznerats walk along the periphery of a flat open field constantly keeping a specific direction,either clockwiseor counterclockwise -- an observationsimilar to that made by Schiorring(1979) in rats treatedwith amphetamine.Our workinghypothesiswas that such edge-bound,unidirectional locanotionreflecteda lateralizedtaxis for edges. Alternatively,it might reflecta directionallateralization, namely, a preferenceto keep a specificloccanotor direction 525
526
M. Pisa and H. Szechtman
relative to the center of the open field, while patrolling its edges. To distinguish among these alternatives, we examined whether the rats kept constant locanotor direction or side of the body exp~ed to edges once the original spatial relation among ostensibly preferred direction and position of the edges relative to the rat's sagittal midline was inverted. Iateralizationof postural support in amorphine-treated rats was investigated by examining whether there was a consistent difference rnnong hindlegs in performing consecutive steps while the alternative hindleg remained rooted during turning in a rotaneter.
Methods Subjects. Thirty male Sprague Dawley rats were obtained from Canadian Breeding Farms. Their body weights ranged frcan225 g to 250 g on their arrival in the laboratory. The rats were housed in groups of three in rodent cages located in a temperature controlled roan with lights on at 07:OO and off at 19:OO daily. Food and water were provided at lib. Q. Apanorphine hydrochloride (Frost Lab.) was dissolved in .9% saline (2.5 rrg/ml), with -1% ascorbic acid added as anti-oxidant, and was injected subcutaneously under the Control injections consisted of the vehicle solution. nape of the neck (1.25 q/kg). Apparatus. The open field consisted of a 180 x 180 an black-painted wooden table, elevated 125 an above the floor, with a removable 50 x 50 cm piece of black-paintedwood making up the central region of the table's surface. The rotcmeter was a hemispheric bowl 60 an in diameter, made of transparent Perspex and placed over a glass surface elevated 150 an above the floor. The recording equipment included a Newvicon videocamera (RCA), a videocassette recorder (Sony, model SL-2500) and a photographic camera (Olympus 0X2). Procedure. Testing started two weeks after the arrival of the rats in the laboratory. In Test 1, the locunotor behavior of the rats was examined in the open field for 1 hr after apomorphine treatment. In Test 2, the rats that had shown edge-bound unidirectional locanotion in Test 1 were re-tested in the open field after injection of amorphine and the re-occurrence of edge-bound unidirectional locomotion was examined in the initial 25 min of the test. Thereafter, the central region of the table's surface was removed, leaving a square hole in the center of the table, and the rats were transported close to an edge of either the table or the hole for choice trials of locanotor direction. At the onset of different trials, the rats were placed on the table with their fronts oriented towards either the center of the table or the clockwise direction or the counterclockwise direction relative to the center of the table. Photographs were taken of the rats' locomotor activity in representative trials. In Test 3, the locomotor behavior of the rats that showed edge-bound unidirectional locomotion in Test 1, and of 12 rats selected at randan fran those that did not, was examined in the rotcmeter for 1 hour after administration of apomorphine. Wenty l-min behavioral samples spaced 2 min apart were videorecorded for later analysis. In each sample, rotational lateralizationwas measured as the difference between 360' clockwise rotations and 360' counterclockwiserotations of the pelvis (net rotations), and lateralization of posture was measured as the difference among the consecutive steps made by each hindleg while the other hindleg stayed rooted (net consecutive steps). In Test 4, the locomotor behavior of the rats was re-examined in the open field after a control injection. All tests were conducted at intervals of at least one week.
Results Apcmorphine-InducedIateralizationof Taxis In Test 1, 5 rats showed edge-bound unidirectional locomotion: starting 5-10 min after the apctnorphinetreatment, 3 such rats constantly walked counterclockwlse and 2 rats clockwise along the perimeter of the open field until the end of the session. The remaining 25 rats either locomoted away from the edges most of the time or showed no clear cut directional preference while walking along edges. In Test 2, all 5 rats showed the same edge-bound unidirectional locomotion in the initial 25 min of the test as they did in Test 1. One such rat with edge-bound, counterclockwise locanotlon is shown in Figure 1.
Lateralizing effects of apomorphine
527
Figure 1. Edge-bound unidirectional locanotion in a rat treated with apomorphine (1.25 m/kg s.c.). The sequence of pictures, fran left top to right bottgn, shows the rat performing its 6th complete counterclockwiseloop along the periphery of the open field 21 min after the injection. Time of day (p.m.) is shown at the bottom right of each picture. Five out of 30 a~or~hine-treaty rats shwed such edge-bound unidirectional locomotion in the open field.
In the choice trials, all 5 rats consistently walked in the originally preferred direction along the edges of the table, and in the opposite direction along the edges of the hole, irrespective of the orientation of their bodies at the onset of the trials. Figure 2 illustrates this finding for the same rat which, as shown in Figure 1, consistently walked counterclockwise along the periphery of the table. It can be seen that this rat walked counterclockwisealong the edges of the table and clockwise along the edges of the hole in the choice trials in which it was released while facing the center of the table. Thus, the rat changed direction of locomotion relative to the center of the table, but it kept constant the side of its body exposed to edges, namely, its right side. The rat also demonstrated such lateralized (right-biased)taxis for edges in the trials in which it was released while it had either its left side or its right side parallel to edges. Thus, in the trials in which the rat's right side was initially parallel to an edge of either the table or the hole, the rat inrnediately proceeded to locanote forward, walking counterclockwisearound the table and clockwise around the hole, respectively. On the other hand, in the trials in which the rat's left side was initially parallel to an edge of either the table or the hole, the rat did not immediately proceed to locomote forward. Instead, it first turned its body until its right side came into contact with the edge, and then it proceeded to walk along it, counterclockwisealong the periphery of the table and clockwise around the hole. In short, while walking along the edges of either the table OK the hole, all 5 rats took such directions as to keep one and the same side of their bodies constantly exposed to demonstrating that the apanorphine-induced, edge-bound unidirectional edges, thus locomotion reflects a lateralization of taxis for edges rather than a directional lateralization. None of the rats show& the phencxnenonof edge-bound unidirectional locomotion in the open field after vehicle injection.
528
M. Pisa and H. Szechtman
Figure 2. Apcmorphine-induced lateralization of taxis for edges. Same rat and test directioneither session as in Figure 1. The rat was given choice trials of loccanotor along the peripheryof the open field (A) or along the edges of a square hole in the middle of the open field (B). At the onset of both types of trials,the rat faced the along the center of the table. Upon being released,the rat walked counterclockuuise perimeterof the table and clockwisealong the perimeterof the hole. Thus, the rat's direction of locanotionaround the hole was opposite that along the peripheryof the table. In contrast,the rat'sbody side exposedto edgeswas the same in both situations, i.e.,the right side. Apanorphine-Induced Iateralization of PosturalSupport Figure 3 shows that out of the 17 rats tested in the rotcmeterafter apcmorphine treatment,14 rats (82%) reliablyfavoureda specifichindlegfor posturalsupportduring turning,6 rats preferrirqthe left hindlegand 8 rats the right hindlegfor support. RelationBetweenApanorphine-Induced Lateralization of Taxis and Rotation Ike of the 5 rats with apanorphine-induced lateralization of taxisand 3 of the 12 rats with no such laterafizationshowed a significantlateralizationof rotation in the
Lateralizing effectsof apomorphine
529
rotolneter; the remainingrats did not (Figure3). A test of independenceindicatedno significantassociationbetweenpresenceor absenceof lateralizedtaxis and presenceor &senc~ of rotationallaralization (p= .47, Fisher'sexact probability).
l.%
0
ROTATIONS
tg
coNsEcunvEsTEps
m
l.&
l
r12
of 17 rats tested in a rotaneter Figure 3. Rotationalard postural lateralizations bars after aporphine treatment(1.25nq/kg s.cg). The open bav and the cross-hatched rotations) representthe mean + SEN net rotations(360 clockwise- 360 counterclockwise and the mean + SE!?net consecutivesteps (consecutivesteps of the right hindleg consecutivesteps of the left hindleg)of individualrats in 20 1-min periods,spaced 2 min apart, after apdmorphineadministration.The bars with heavier lines representrats with apanorphine-induced lateralization of taxis, as revealedby the open fields tests significantasymnetries(p < illustratedin Figures1 and 2. Stars indicatestatistically -05 or less, two-tailed, paired t tests). The insetsummarizesthe incidenceof ratswith or without statistically signifEant lateralizations of rotationand posture. A test of independenceindicatedno significantassociationbetween the two phenanena (p= .32, Fisher'sexact probability). panorphine_Irduced RelationBetweenA
rt and Rotation
The inset in Figure3 smmarizes the relationamong incidenceof posturallateralization and incidence of rotational lateralization. All 5 rats with reliable rotational lateralizationalso showed a reliable postural lateralization.Thus, the lateralized rotationwas a reliablepredictorof lateralizedpostural. support (p= .031, one-tailed binanial test). CRY the other hand, the lateralization of pstural supportwas not a reliablepredictorof lateralizedrotation(p= .21):only 5 out of 14 rats with a reliable postural lateralizationalso showed a reliably lateralized rotation. A test of independenceshowed no consistentassociationsnnongthe Wo phenanena(p= -32, Fisher's exact probability).There was a significantpositivecorrelation,however,m-nor-q number of net rotationsand number of net consecutivesteps of individualrats (r= .62, p < .OOOl).
530
M. Pisa and H. Szechtman
Discussion The present findings provide the first demonstration that systemic activation of dopamine receptors by apomorphine can induce lateralizationsof taxis and postural support in intact rats. If it is assumed that a taxis for edges involves the operation of an attentional process, then the results of Tests 1 and 2 may be interpreted to indicate that systemic activation of dopamine receptors can induce compulsive and strongly lateralized attention in rats. Other investigators have reported qualitative observations of lateralized postural support in rats treated with dopamincsnimeticdrugs after unilateral lesions of the dopaminergic nigrostriatal pathway (Ungerstedtand Arbuthnott, 1970). The results of Test 3 provide the first quantitative demonstration that apanorphine induces a reliable lateralization of postural support in many intact rats (82% of the sample). Our results also confirm those of previous studies (Jexand Glick, 1976) that apcmorphine can induce a reliable lateralization of rotation in sane intact rats (28% of the sample, in the present study). The lack of statistically significant dependence among lateralized taxis for edges and lateralized rotation may be interpreted to indicate that these effects of amorphine are independent of each other. However, it remains to be examined whether a lateralized orientation to stimuli other than ed.gesplays a role in the phenanenon of lateralized rotation. The lack of statistically significant dependence between the lateralizing effects of apomorphine on posture and rotation does not appear to support the hypothesis of a tight mechanistic relation between these behavioral phenomena. However, a reliable correlation was found between the magnitudes of these lateralizationeffects. The present study does not establish whether this correlation reflects a causal relation. The neural mechanisms of the lateralization effects of apomorphine in intact rats are not known. A plausible hypothesis is that endogenous interhemispheric asymmetries of dopamine-receptorresponsiveness in functionallydistinctive brain regions account for the different types of apunorphine-induced lateralizations found in individual rats. This hypothesis warrants further studies.
Conclusions Systemic activation of dopamine receptors by apcmorphine can induce lateralizations of taxis, postural support and rotation in intact rats. Reliable lateralizations of either taxis for edges or postural support are not closely coupled with lateralized rotation.
Acknowledganent Supported by funds fran the Medical Research Council (MA-8115 to M.P.) and the National Sciences and Engineering Research Council (A0544 to H.S.). M. Pisa holds a Scholarship of The Ontario Mental Health Foundation and H. Szechtrnana Scholarship of the Medical Research (buncil.
References JERDSSI, T.P. and GLICK, S.D. (1976) Drug-induced rotation in rats without lesions: behavioral and neurochemical indices of a normal asynnnetryin nigro-striatal function. Psychopharmacol.47: 249-260. and GAJDA, L. (1972) Effect of amorphine on motility in rats. MAJ, J., GRABCWSKA>. Eur. J. Pharmacol. -17: 208-214.
Lateralizing effects of apomorphine
531
RANDRUP, A., MUNKVAD, I. and LJLGEN, P. (1963) Adrenergic mechanisn and anphetmine induced abnormal behavior. Acta Phannacol. Toxicol. 20: 145-147. SCHIORRING, E. (1979) An open field study of stereotyped locanotor activity in amphetamine-treatedrats. Psychophannacol. 66: 281-287. UNGERSTEDT, U. and ARBIJTHNCYTT, G.W. (1970) Quztitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal system. Brain Res. -24: 485-493.
Inquiries and reprint requests should be addressed to: Dr. Michele Pisa Department of Neurosciences McMaster University Hamilton, Ontario, L8N 325, Canada
LATERALIZING
027&5846/85 $0.00 + .50 Copyright @ 1985 Pergamon Press Ltd.
EFFECTS OF APOMORPHINE ON TAXIS, POSTURAL SUPPORT AND ROTATION IN RATS
MICHEIEPISAl'*and HENRY SZECHWIAN1 and 2Psychiatry %a partientof Neurosciences McMasterUniversity, Hamilton,Ontario,Canada (Finalform, July 1985) Abstract Pisa, Michele and Henry Szechtman:Lateralizing effectsof apcxnorphine on taxis,postural supportand rotationin rats. Prog. Neuro-Psychopharmacol. & Biol. Psychiat.1985,-9 (5/6):525-531. 1. Subcutaneous injections of apunorphine,a dopamine receptor agonist, induced a lateralization of taxis for edges in 16% of rats and a reliablelateralization of posturalsupportin 82% of rats. 2. The relation among these effects and the lateralizingeffects of aptmorphineon rotationalbehaviorwere examined. Lateralizedrotationdid not reliablycorrelate with lateralizedtaxis. HOwever,it correlatedwith a relativelylarge asymmetryof posturalsupport. 3. The lateralizingeffectsof apanorphineon taxisand rotationmay reflectattentional and directionalasymmetries, respectively.It is proposedthat apcmorphinecan induce differenttypes of lateralizations, includingattentional,posturaland directional, and that the lateralizingeffectsof apcmorphineon postureand locanotordirection are interrelated.Regionalbrain interhemispheric asynmetriesin the responsiviness of dopamine receptors may underlie different types of apcmorphine-induced lateralizations. Keywords: apcmorphine, dopamine,lateralization, taxis,posture,rotation,attention. Introduction tqoamincmimetic drugs such as amphetamineor apanorphine can increaselocanotionin rats (Maj et al., 1972; Rardrupet al., 1963). This effect is often attendedby a preference to turn in a specificdirection(Jerussiand Glick, 1976). There is evidencesuggesting that an asymmetricalactivationof striataldopaminergictransmission accountsfor such lateralization of turning (Jerussiand Glick, 1976). The behavioralmechanismof this phencmenonis still controversial, however. The lateralizedturningmight reflecteither a spatiallateralization, namelya preferenceof locanotordirectionunrelatedto specific externalstimuli,or a lateralization of taxis, namely,a preferenceto move in relation to specificstimuli locatedon a specificside of the body, or a posturallateralization, namely,a preferenceto use a specifichindlq for posturalsupportand the other hindleg for stepping,or a ccrnbination of these. There is no direct evidence,however,as to whether or not dopaminanimetic drugs have lateralizing effectson any of thesebehavioral processes. Thus, a study to this effect would be the prerequisite step toward understandingthe functionalbasis of the lateralization of turning. Accordingly,the primary objective of this study was to exmnine whether peripheraladministrationof apanorphine,a dopaminereceptoragonist,can indeed induce lateralizations of taxis and posturalsupport. To examine lateralization of taxis,we proceededfrom the preliminaryobservationthat, after doses of amorphine that elicithyperlocanotion, scznerats walk along the periphery of a flat open field constantly keeping a specific direction,either clockwiseor counterclockwise -- an observationsimilar to that made by Schiorring(1979) in rats treatedwith amphetamine.Our workinghypothesiswas that such edge-bound,unidirectional locanotionreflecteda lateralizedtaxis for edges. Alternatively,it might reflecta directionallateralization, namely, a preferenceto keep a specificloccanotor direction 525
526
M. Pisa and H. Szechtman
relative to the center of the open field, while patrolling its edges. To distinguish among these alternatives, we examined whether the rats kept constant locanotor direction or side of the body exp~ed to edges once the original spatial relation among ostensibly preferred direction and position of the edges relative to the rat's sagittal midline was inverted. Iateralizationof postural support in amorphine-treated rats was investigated by examining whether there was a consistent difference rnnong hindlegs in performing consecutive steps while the alternative hindleg remained rooted during turning in a rotaneter.
Methods Subjects. Thirty male Sprague Dawley rats were obtained from Canadian Breeding Farms. Their body weights ranged frcan225 g to 250 g on their arrival in the laboratory. The rats were housed in groups of three in rodent cages located in a temperature controlled roan with lights on at 07:OO and off at 19:OO daily. Food and water were provided at lib. Q. Apanorphine hydrochloride (Frost Lab.) was dissolved in .9% saline (2.5 rrg/ml), with -1% ascorbic acid added as anti-oxidant, and was injected subcutaneously under the Control injections consisted of the vehicle solution. nape of the neck (1.25 q/kg). Apparatus. The open field consisted of a 180 x 180 an black-painted wooden table, elevated 125 an above the floor, with a removable 50 x 50 cm piece of black-paintedwood making up the central region of the table's surface. The rotcmeter was a hemispheric bowl 60 an in diameter, made of transparent Perspex and placed over a glass surface elevated 150 an above the floor. The recording equipment included a Newvicon videocamera (RCA), a videocassette recorder (Sony, model SL-2500) and a photographic camera (Olympus 0X2). Procedure. Testing started two weeks after the arrival of the rats in the laboratory. In Test 1, the locunotor behavior of the rats was examined in the open field for 1 hr after apomorphine treatment. In Test 2, the rats that had shown edge-bound unidirectional locanotion in Test 1 were re-tested in the open field after injection of amorphine and the re-occurrence of edge-bound unidirectional locomotion was examined in the initial 25 min of the test. Thereafter, the central region of the table's surface was removed, leaving a square hole in the center of the table, and the rats were transported close to an edge of either the table or the hole for choice trials of locanotor direction. At the onset of different trials, the rats were placed on the table with their fronts oriented towards either the center of the table or the clockwise direction or the counterclockwise direction relative to the center of the table. Photographs were taken of the rats' locomotor activity in representative trials. In Test 3, the locomotor behavior of the rats that showed edge-bound unidirectional locomotion in Test 1, and of 12 rats selected at randan fran those that did not, was examined in the rotcmeter for 1 hour after administration of apomorphine. Wenty l-min behavioral samples spaced 2 min apart were videorecorded for later analysis. In each sample, rotational lateralizationwas measured as the difference between 360' clockwise rotations and 360' counterclockwiserotations of the pelvis (net rotations), and lateralization of posture was measured as the difference among the consecutive steps made by each hindleg while the other hindleg stayed rooted (net consecutive steps). In Test 4, the locomotor behavior of the rats was re-examined in the open field after a control injection. All tests were conducted at intervals of at least one week.
Results Apcmorphine-InducedIateralizationof Taxis In Test 1, 5 rats showed edge-bound unidirectional locomotion: starting 5-10 min after the apctnorphinetreatment, 3 such rats constantly walked counterclockwlse and 2 rats clockwise along the perimeter of the open field until the end of the session. The remaining 25 rats either locomoted away from the edges most of the time or showed no clear cut directional preference while walking along edges. In Test 2, all 5 rats showed the same edge-bound unidirectional locomotion in the initial 25 min of the test as they did in Test 1. One such rat with edge-bound, counterclockwise locanotlon is shown in Figure 1.
Lateralizing effects of apomorphine
527
Figure 1. Edge-bound unidirectional locanotion in a rat treated with apomorphine (1.25 m/kg s.c.). The sequence of pictures, fran left top to right bottgn, shows the rat performing its 6th complete counterclockwiseloop along the periphery of the open field 21 min after the injection. Time of day (p.m.) is shown at the bottom right of each picture. Five out of 30 a~or~hine-treaty rats shwed such edge-bound unidirectional locomotion in the open field.
In the choice trials, all 5 rats consistently walked in the originally preferred direction along the edges of the table, and in the opposite direction along the edges of the hole, irrespective of the orientation of their bodies at the onset of the trials. Figure 2 illustrates this finding for the same rat which, as shown in Figure 1, consistently walked counterclockwise along the periphery of the table. It can be seen that this rat walked counterclockwisealong the edges of the table and clockwise along the edges of the hole in the choice trials in which it was released while facing the center of the table. Thus, the rat changed direction of locomotion relative to the center of the table, but it kept constant the side of its body exposed to edges, namely, its right side. The rat also demonstrated such lateralized (right-biased)taxis for edges in the trials in which it was released while it had either its left side or its right side parallel to edges. Thus, in the trials in which the rat's right side was initially parallel to an edge of either the table or the hole, the rat inrnediately proceeded to locanote forward, walking counterclockwisearound the table and clockwise around the hole, respectively. On the other hand, in the trials in which the rat's left side was initially parallel to an edge of either the table or the hole, the rat did not immediately proceed to locomote forward. Instead, it first turned its body until its right side came into contact with the edge, and then it proceeded to walk along it, counterclockwisealong the periphery of the table and clockwise around the hole. In short, while walking along the edges of either the table OK the hole, all 5 rats took such directions as to keep one and the same side of their bodies constantly exposed to demonstrating that the apanorphine-induced, edge-bound unidirectional edges, thus locomotion reflects a lateralization of taxis for edges rather than a directional lateralization. None of the rats show& the phencxnenonof edge-bound unidirectional locomotion in the open field after vehicle injection.
528
M. Pisa and H. Szechtman
Figure 2. Apcmorphine-induced lateralization of taxis for edges. Same rat and test directioneither session as in Figure 1. The rat was given choice trials of loccanotor along the peripheryof the open field (A) or along the edges of a square hole in the middle of the open field (B). At the onset of both types of trials,the rat faced the along the center of the table. Upon being released,the rat walked counterclockuuise perimeterof the table and clockwisealong the perimeterof the hole. Thus, the rat's direction of locanotionaround the hole was opposite that along the peripheryof the table. In contrast,the rat'sbody side exposedto edgeswas the same in both situations, i.e.,the right side. Apanorphine-Induced Iateralization of PosturalSupport Figure 3 shows that out of the 17 rats tested in the rotcmeterafter apcmorphine treatment,14 rats (82%) reliablyfavoureda specifichindlegfor posturalsupportduring turning,6 rats preferrirqthe left hindlegand 8 rats the right hindlegfor support. RelationBetweenApanorphine-Induced Lateralization of Taxis and Rotation Ike of the 5 rats with apanorphine-induced lateralization of taxisand 3 of the 12 rats with no such laterafizationshowed a significantlateralizationof rotation in the
Lateralizing effectsof apomorphine
529
rotolneter; the remainingrats did not (Figure3). A test of independenceindicatedno significantassociationbetweenpresenceor absenceof lateralizedtaxis and presenceor &senc~ of rotationallaralization (p= .47, Fisher'sexact probability).
l.%
0
ROTATIONS
tg
coNsEcunvEsTEps
m
l.&
l
r12
of 17 rats tested in a rotaneter Figure 3. Rotationalard postural lateralizations bars after aporphine treatment(1.25nq/kg s.cg). The open bav and the cross-hatched rotations) representthe mean + SEN net rotations(360 clockwise- 360 counterclockwise and the mean + SE!?net consecutivesteps (consecutivesteps of the right hindleg consecutivesteps of the left hindleg)of individualrats in 20 1-min periods,spaced 2 min apart, after apdmorphineadministration.The bars with heavier lines representrats with apanorphine-induced lateralization of taxis, as revealedby the open fields tests significantasymnetries(p < illustratedin Figures1 and 2. Stars indicatestatistically -05 or less, two-tailed, paired t tests). The insetsummarizesthe incidenceof ratswith or without statistically signifEant lateralizations of rotationand posture. A test of independenceindicatedno significantassociationbetween the two phenanena (p= .32, Fisher'sexact probability). panorphine_Irduced RelationBetweenA
rt and Rotation
The inset in Figure3 smmarizes the relationamong incidenceof posturallateralization and incidence of rotational lateralization. All 5 rats with reliable rotational lateralizationalso showed a reliable postural lateralization.Thus, the lateralized rotationwas a reliablepredictorof lateralizedpostural. support (p= .031, one-tailed binanial test). CRY the other hand, the lateralization of pstural supportwas not a reliablepredictorof lateralizedrotation(p= .21):only 5 out of 14 rats with a reliable postural lateralizationalso showed a reliably lateralized rotation. A test of independenceshowed no consistentassociationsnnongthe Wo phenanena(p= -32, Fisher's exact probability).There was a significantpositivecorrelation,however,m-nor-q number of net rotationsand number of net consecutivesteps of individualrats (r= .62, p < .OOOl).
530
M. Pisa and H. Szechtman
Discussion The present findings provide the first demonstration that systemic activation of dopamine receptors by apomorphine can induce lateralizationsof taxis and postural support in intact rats. If it is assumed that a taxis for edges involves the operation of an attentional process, then the results of Tests 1 and 2 may be interpreted to indicate that systemic activation of dopamine receptors can induce compulsive and strongly lateralized attention in rats. Other investigators have reported qualitative observations of lateralized postural support in rats treated with dopamincsnimeticdrugs after unilateral lesions of the dopaminergic nigrostriatal pathway (Ungerstedtand Arbuthnott, 1970). The results of Test 3 provide the first quantitative demonstration that apanorphine induces a reliable lateralization of postural support in many intact rats (82% of the sample). Our results also confirm those of previous studies (Jexand Glick, 1976) that apcmorphine can induce a reliable lateralization of rotation in sane intact rats (28% of the sample, in the present study). The lack of statistically significant dependence among lateralized taxis for edges and lateralized rotation may be interpreted to indicate that these effects of amorphine are independent of each other. However, it remains to be examined whether a lateralized orientation to stimuli other than ed.gesplays a role in the phenanenon of lateralized rotation. The lack of statistically significant dependence between the lateralizing effects of apomorphine on posture and rotation does not appear to support the hypothesis of a tight mechanistic relation between these behavioral phenomena. However, a reliable correlation was found between the magnitudes of these lateralizationeffects. The present study does not establish whether this correlation reflects a causal relation. The neural mechanisms of the lateralization effects of apomorphine in intact rats are not known. A plausible hypothesis is that endogenous interhemispheric asymmetries of dopamine-receptorresponsiveness in functionallydistinctive brain regions account for the different types of apunorphine-induced lateralizations found in individual rats. This hypothesis warrants further studies.
Conclusions Systemic activation of dopamine receptors by apcmorphine can induce lateralizations of taxis, postural support and rotation in intact rats. Reliable lateralizations of either taxis for edges or postural support are not closely coupled with lateralized rotation.
Acknowledganent Supported by funds fran the Medical Research Council (MA-8115 to M.P.) and the National Sciences and Engineering Research Council (A0544 to H.S.). M. Pisa holds a Scholarship of The Ontario Mental Health Foundation and H. Szechtrnana Scholarship of the Medical Research (buncil.
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Lateralizing effects of apomorphine
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Inquiries and reprint requests should be addressed to: Dr. Michele Pisa Department of Neurosciences McMaster University Hamilton, Ontario, L8N 325, Canada