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Arousal of consummatory behavior in rabbits by single waves of cortical spreading depression
Physiology and Behavior. Vol. 7, pp. 595--599. Pergamon Press, 1971. Printed in Great Britain
Arousal of Consummatory Behavior in Rabbits by Single Waves of Cortical Spreading Depression J O S E P H P. H U S T O N ~ A N D G U S T A V B R O ~ E K
Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia (Received 15 F e b r u a r y 1971) HUSTON,J. P. ANDG. BRO~EK. Arousalof consummatory behaviorin rabbitsby single wavesof corticalspreading depression. PaYSIOL. BEHAV. 7 (4) 595-599, 1971.--Single waves of unilateral cortical spreading depression were triggered by injecting small amounts of KCi solution through cannulae into either the frontal or occipital cortices of rabbits. The animals were prepared chronically for recording of cortical and hippocampal EEG and D-C steady potential shifts. Waves of spreading depression were frequently accompanied by behavioral arousal and the initiation of eating behavior. This concurs with similar results of electrophoretic injection of K+ ions into the occipital cortices of rats. The distribution of onset times of eating, however, was considerably flatter than that found in rats. No significant differences were apparent between mean onset times of behavior induced by occipital and frontal injection of KCI. Potassium
Cortical spreading depression
Arousal
Eating
INJECTION OF small amounts of potassium into or onto the cortex can trigger a wave of massive neuronal depolarization that spreads at a rate of between 2 and 5 mm/min over the cortical hemisphere. The initial depolarization is followed by a longer lasting depression of E E G activity, evoked responses, and various behaviors; hence, the phenomenon is called cortical spreading depression (CSD) [6, 17]. Although CSD is generally known for its inhibitory effects on behavior, it was recently shown to have energizing consequences as well [16]. The electrophoretic injection of K+ ions into the occipital cortices of rats under certain conditions released motor activity as well as eating and drinking behavior about 5 min after initiation of a wave of CSD. The present study was designed to test the generality of this phenomenon by using rabbits instead of rats and by using pressure injection of KCI solution instead of electrophoresis to initiate a wave of spreading depression. Also, due to the larger size of the rabbit brain we expected to find differences in the onset times and patterning of the induced behaviors as a function of frontal and occipital cortical injection of KCI, which would point to critical cortical areas involved in the activation of the behaviors.
Rabbits
according to the scheme of Fig. 1, which shows idealized coordinates of the rabbit brain according to the atlas of Monnier and Gangloff [18]. F o u r injection cannula guides (20 ram long, internal diameter 0.6 Irma) were situated flush with the dura, over the frontal and occipital cortices. Two bipolar, teflon coated, silver, a.c. recording electrodes, 0.25 mm tip diameter, were placed into the dorsal hippocampi (with coordinates from bregma, 4 mm lateral, 4 nun posterior, and 7.5 m m inferior, perpendicular to the skull). Four glass capillary d.c. recording electrodes were placed 5-6 mm lateral from bregma into the frontal and posterior cortices (1 m m anterior and 12 m m posterior, respectively). The capillaries contained agar soaked with 20 % NaCI solution, and a chloridized silver spiral. A common Ag-AgCI screw electrode was placed about 13 m m anterior to bregma. These components were cemented to the skull with dental acrylic.
Procedure The rabbits were tested in transparent experimental boxes, that were 43 cm long, 28 cm wide, with 25 cm high wails, and totally open on top. The animals actually lived in these boxes, some throughout the whole experiment, and hence, were totally adapted to the experimental situation. They always had food available in the box, which consisted of whole carrots and/or solid Larsen pellets. Six per cent KCI solution was injected into the cortices via small eannula~ (dia. external 0.5 ram, internal 0.2 mm) by
METHOD
Animals and implantation Six rabbits, weighing between 2 and 3 kg, were anaesthetized with pentobarbitone and ether, and surgically prepared
xJPH was supported in part by a National Academy of Sciences-Czechoslovak Academy of Sciences exchange fellowship, and subsequently by a National Institute of Mental Health postdoctoral fellowship. Now at the Institute of Pharmacology, University of Ziirich, Gloriastrasse 32, Zfirich Switzerland. 2We thank Dr. Jan Bureg, in whose laboratory this work was done. 595
596
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An animal had to abstain from eating for at least 5 rain before a KCI injection was administered. In practice, the periods of zero eating that preceded KCI injections varied up to several hours, with typical intervals of from 20-40 rain between trials. Hence, at the time of each trial the rabbits were in a state of acute satiation. An animal was generally given no more than 5 trials per day of testing. The onset and duration of the monitored behavior of the animals was either marked on the EEG records with a handoperated event recorder, or, in most cases, registered by means of stop watches. During most experimental sessions only food was made available to the rabbit, hence, the data consisted mainly of eating behavior.
ZX
RESULTS
FIG. 1. Idealized rabbit brain according to Monnier and Gangloff [18], with positions of recording electrodes and injection cannulae. way of polyethylene tubing which extended from a microsyringe. The KCI was always applied unilaterally on any given trial. One ttl KCI was generally sufficient to trigger a wave of spreading depression, although at times up to 5 t~l were necessary. An eight channel polygraph was used for recording purposes. Cortical and hippocampal EEG and steady potential changes were recorded on only a portion of the trials, since the leads somewhat interfered with free head movement of the rabbits.
Of the six rabbits tested, it was possible to elicit eating by cortical spreading depression in 9 hemispheres of 5 rabbits. Figure 2 shows a portion of a recording taken during a single wave of spreading depression induced by injection of KCI into a frontal cortex. The top trace of each of the 3 rows indicates the time since injection (0 min) of KCI. The second trace (I-Hip) represents hippocampal EEG from the side ipsilateral to the depressed hemisphere. The third trace (C-Co) is the cortical EEG from the nondepressed contralateral hemisphere. The fourth trace represents the ipsilateral cortical steady potential change that accompanies the wave of spreading depression. It shows the peak negativity at the frontal electrode (upward excursion) to be about 5 mV at about 1.4 min after injection, and peak negativity at the posterior electrode (downward deflection) to occur about 3.6 min after injection. fmia
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FIG. 2. Polygraph recording of EEG and D-C potentials during a single wave of spreading depression induced by anterior cortical KCI injection. EEG was recorded from dorsal hippocampus ipsilateral to the depressed hemisphere (I-Hip), and from the nondepressed cortex (G-Co). I - D e represents the steady potential change recorded from the depressed cortex (an upward excursion is negativity at the frontal electrode; a downward deflection is negativity at the posterior pole). Note the onset of eating and correlated EEG changes at 2.4 rain after injection of KCI.
CSD AND CONSUMMATORY BEHAVIOR
597
Eating in this case, began about 2.5 min after injection of KCI (see row B) and lasted until 4 min after injection. Note the hippocampal synchronization (theta activity) that accompanies the onset and duration of eating behavior. The top histogram of Fig. 3 shows the distribution of onset times of 77 cases of eating induced by cortical spreading depression in 5 rabbits. Onset of eating was most probable (26 % of the time) between 4 and 6 min after injection of KCI. About 85 per cent of the elicited eating commenced within the first 8 min of the initiation of spreading depression. The bottom histogram of Fig. 3 represents the incidence of eating during the trials when eating was elicited by CSD. F o r example, in about 28 per cent of the positive trials some eating was observed to occur between 6 a n d 8 min after injection, the period of highest incidence of observed eating. The
incidence of eating was satisfactorily recorded only during 56 trials. The duration of the eating bouts ranged from a few bites to l0 min of continuous biting and chewing, with an overall mean of 2.2 min, and a range of means from 0.64 to 3.4 min for the 5 rabbits. These histograms represent the combined data for cortical spreading depression induced in the occipital and frontal cortices. Since we expected to find differences in the onset distributions of eating between frontal and occipital cortical injections, the data were redrawn according to Fig. 4, which shows the histograms of the onset distributions of eating induced by frontal (top) and occipital (bottom) injections. Unexpectedly, the onset distributions were very similar, with no significant difference between the rncans, 4.4 min vs. 5.3 rain respectively, for anterior and posterior injection. The incidence of elicited eating in those rabbits in which it could be demonstrated approximated 50 per cent of trials. During some sessions eating was elicited on 100 per cent of the
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FIG. 3. Top: histogram showing distribution of onset times of 77 cases of eating (,~ 50 per cent of trials) induced by cortical spreading depression in 5 rabbits. Zero min represents time of KC1 injection. Dotted line is the arithmetic mean. Bottom: histogram showing the incidence of observed eating throughout spreading depression in 56 trials.
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FIG. 4. Histograms of distributions of onset times of eating elicited by injection of KC1 into anterior (top) and posterior (bottom) cortices of 5 rabbits. Zero min represents time of KCI injection. Dotted lines indicate arithmetic means.
598
HUSTON AND BRO~.EK
trials. These estimates are biased, however, since, due to the metabolic and behavioral exhaustion that takes place with cumulative effects of CSD [6], a session was terminated when an animal failed to respond several times in succession. On about 25 per cent of the trials the KCI injections were apparently subthreshold and did not trigger a wave of spreading depression. On such occasions eating was observed to occur within 15 rain of the injection on 7 per cent of the trials. This indicates that the elicited eating on the successful trials was due principally to properties of the CSD rather than some other effect of the KCI injection. One animal, who was tested with water in the box, exhibited SD-induced drinking and/or eating. All cases of elicited eating were accompanied and often preceded by other signs of behavioral arousal, such as turning in a circle, raising the ears, orienting responses, and digging movements. Other behavior that was frequently observed during CSD was yawning and stretching.
DISCUSSION
The elicitation of eating, locomotion and orienting behavior in rabbits by single waves of CSD, and the occurrence of yawning responses, concur with the earlier data on rats [15, 16]. One important difference between the procedures used is that in the present study waves of CSD were administered by injecting KCI solution through implanted cannulae rather than by electrophoretic injection of K ÷ ions. This rules out an explanation of the induced behavior as an aftereffect of the current passed through the brain. A discrepancy between the results with rabbits and those with rats is the comparative flatness of the onset distribution of induced eating found in the present study when the data were averaged across rabbits. A possible explanation is the difference in behaviors required in the two situations. The rats had to perform relatively complex locomotor and orienting movements in order to eat or to lick at the water spout, whereas the rabbits merely required movement of the head to reach the food source. On the other hand, the somewhat flat distribution and failure to find differences in mean onset times between frontal and occipital injections suggests an explanation of the behavioral effects in terms of the general arousal reactions that accompany CSD. F o r example, single waves of CSD, triggered in one hemisphere of rats, are accompanied by
cortical arousal (EEG desynchronization) in the contralateral hemisphere [4, 28]. A variety of manipulations that presumably arouse the animal can facilitate operant responding [11], copulation [3, 7], as well as food and water intake [1, 22, 26] in rats. Arousal may account for the CSD-elicited behavior in tote, or at least in part. Relevant in this context is the hypothesis that displacement activities serve to decrease the level of arousal [9], andthe somewhat relatedconcept of adjunctive behavior, as espoused recently [12, 27] for displacement behaviors that occur under intense motivational conditions. An alternate hypothesis, proposed earlier [16], is that the effect reflects cortical-subcortical interactions and that the induced behavior is the result of activation of subcortical circuits involved in motivated behaviors that are modulated by cortical activity. This possibility can not be ruled out, especially since CSD has been shown to interact with hypothalamic mechanisms in a variety of ways, such as by attenuation of hypothalamic noradrenaline [10], EEG [29], evoked potentials [21], activity of single units [5], electrical selfstimulation [5, 20], and electrically elicited eating and drinking [14]; as well as by causing a relapse of hypothalamic lesioninduced aphagia after partial recovery [2, 25]. Subthreshold quantities of KCI that did not trigger CSD were seldom followed by eating. Elsewhere, both drinking and eating have been induced in goats by infusing larger amounts of hypertonic KCI solution into the 3rd ventricle [19]. Hence, it may be that in the present experiment a similar effect was occasioned by the increase in extracellular K + concentration accompanying the massive neuronal depolarization that precedes SD. Other sources support the conjecture that cortical spreading depression can energize certain behaviors. F o r example, Suzuki and Uneoka [24] noted "circus movements, exploratory behavior and alimentary behavior such as chewing and gnawing" during CSD in some rabbits. Bilateral cortical application of KCI has been shown to facilitate lordosis responses in female rats [8]. Unpublished data by Huston and Bureg suggests that striatal SD in chickens can elicit pecking of grain, and that caudate SD in rats energizes eating and drinking. Similarly, Stille and Sayers [23] have shown caudate SD to induce gnawing, licking and locomotor responses. Also the bursting of licking, wheel running and Sidman avoidance observed by Freedman [13], presumably during multiple waves of CSD induced by placing KCI solution onto the dura, may reflect the elicitation as well as recovery of the behaviors.
REFERENCES
1. Amsel, A. and I. Maltzman. The effect upon generalized drive strength of emotionality as inferred from the level of consummatory response. J. exp. Psychol. 40: 563-569, 1950. 2. Balinska, H., O. Bure~owl and E. Fifkova. The influence of cortical and thalamic spreading depression on feeding behavior of rats with lateral hypothalamic lesions. Acta Biol. exp. (Warsaw) 27: 355-363, 1967. 3. Bartiold, R. J. and R. D. Sachs. Sexual behavior: stimulation by painful electric shock to the skin of male rats. Science 161 : 392-394, 1968. 4. Bro~k,G. QuantitativeanalysisofEEGchangesaccompanying unilateral cortical spreading depression in freely moving rats, in preparation. 5. Bur~, J., O. Bure~owi, E. Fifkova, J. Olds, M. E. Olds and R. P. Travis. Spreading depression and subcortical drive centres. Physiologia bohemoslov. 10: 321-331, 1961.
6. Bureg, J., O. Bure~ov~t and J. Kfivanek. The Mechanism and Application of Le~o's Spreading Depression. Academic Press, in press. 7. Caggiula, A. R. and R. Eibergen. Copulation of virgin male rats evoked by painful peripheral stimulation. J. comp. physiol. Psychol. 69: 414-419, 1969. 8. Clemens, L. G., K. Wallen and R. A. Gorski. Mating behavior: facilitation in the female rat after cortical application of potassium chloride. Science 157: 1208-1209, 1967. 9. Delius, J. D. Displacement activities and arousal. Nature (London) 214: 1259--1260, 1967. 10. Donoso, A. O. Cortical "spreading depression" and hypothalamic noradrenaline. Actaphysiol. latinoam. 14: 399--400, 1964. 11. Dureharme, R. and D. Belanger. Influence d'une stimulation electrique sur le niveau d'activation. Can. J. Psychol. 15: 16-68, 1961.
CSD AND CONSUMMATORY BEHAVIOR 12. Falk, J. L. Conditions producing psychogenic polydipsia in animals. Ann. N.Y. Acad. ScL 157: 569-593, 1969. 13. Freedman, N. L. Recurrent behavioral recovery during spreading depression. J. comp. physiol. Psychol. 68: 210-214, 1969. 14. Huston, J. P. Effect of cortical spreading depression on behavior elicited by electric hypothalamic stimulation. From the Proceedings of the XXV International Congress of Physiological Sciences, Munich, July 1971. 15. Huston, J. P. Yawning and penile erection in rats induced by cortical spreading depression. Nature (Lond.), 232:274-275 1971. 16. Huston, J. P. and J. Buret. Drinking and eating elicited by cortical spreading depression. Science 169: 702-704, 1970. 17. Le~o, A. A. P. Spreading depression of activity in the cerebral cortex. J. Neurophysiol. 7: 359-390, 1944. 18. Monnier, M. and H. Gangloff. Atlas for Stereotaxic Brain Research on the Conscious Rabbit. Amsterdam: Elsevier Publishing Co., 1961. 19. Olsson, K. Effects of slow infusion of KCI into the 3rd brain ventricle. Acta physiol, scand. 77: 358-364, 1969. 20. Riidiger, W. and E. Fifkova. Operant behavior and subcortical drive during spreading depression. J. comp. physiol. Psychol. 56: 375-379, 1963. 21. Santibafiez-H. G. and S. Espinoza. Cortico-hypothalamic interaction in cats. Acta Biol. exp. (Warsaw) 28: 83-92, 1968.
599 22. Siegel, P. S. and J. J. Brantley. The relationship of emotionality to the consummatory response of eating. J. exp. Psychol. 42: 304-306, 1951. 23. Stille, G. and A. Sayers. Effect of a striatal spreading depression on the pharmacogenic catatonia. Int. J. Neuropharm. g: 181-189, 1969. 24. Suzuki, H. and K. Uneoka. Effect of cortical spreading depression on operant behavior in the rabbit. Physiol. Behav. 1: 301-304, 1966. 25. Teitelbaum, P. and J. Cytawa. Spreading depression and recovery from lateral hypothalamic damage. Science 147: 61-63, 1965. 26. Ullman, A. D. Three factors involved in producing "compulsive eating" in rats. J. comp. physiol. Psychol. 45: 490-496, 1952. 27. Wayner, M. J. Motor control functions of the lateral hypoththalamusandadjunctivebehavior. Physiol.Behav.5: 1319-1325, 1970. 28. Weiss, T. Short-lasting cortical desynchronization in the course of the propagation of spreading EEG depression in one hemisphere. Physiologia Bohemoslov. 10: 27-35, 1961. 29. Weiss, T. and E. Fifkova. Bioelectric activity in the thalamus and hypothalamus of rats during cortical spreading EEG depression. Electroenceph. Clin. Neurophysiol. 13: 734-744, 1961.
Arousal of Consummatory Behavior in Rabbits by Single Waves of Cortical Spreading Depression J O S E P H P. H U S T O N ~ A N D G U S T A V B R O ~ E K
Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia (Received 15 F e b r u a r y 1971) HUSTON,J. P. ANDG. BRO~EK. Arousalof consummatory behaviorin rabbitsby single wavesof corticalspreading depression. PaYSIOL. BEHAV. 7 (4) 595-599, 1971.--Single waves of unilateral cortical spreading depression were triggered by injecting small amounts of KCi solution through cannulae into either the frontal or occipital cortices of rabbits. The animals were prepared chronically for recording of cortical and hippocampal EEG and D-C steady potential shifts. Waves of spreading depression were frequently accompanied by behavioral arousal and the initiation of eating behavior. This concurs with similar results of electrophoretic injection of K+ ions into the occipital cortices of rats. The distribution of onset times of eating, however, was considerably flatter than that found in rats. No significant differences were apparent between mean onset times of behavior induced by occipital and frontal injection of KCI. Potassium
Cortical spreading depression
Arousal
Eating
INJECTION OF small amounts of potassium into or onto the cortex can trigger a wave of massive neuronal depolarization that spreads at a rate of between 2 and 5 mm/min over the cortical hemisphere. The initial depolarization is followed by a longer lasting depression of E E G activity, evoked responses, and various behaviors; hence, the phenomenon is called cortical spreading depression (CSD) [6, 17]. Although CSD is generally known for its inhibitory effects on behavior, it was recently shown to have energizing consequences as well [16]. The electrophoretic injection of K+ ions into the occipital cortices of rats under certain conditions released motor activity as well as eating and drinking behavior about 5 min after initiation of a wave of CSD. The present study was designed to test the generality of this phenomenon by using rabbits instead of rats and by using pressure injection of KCI solution instead of electrophoresis to initiate a wave of spreading depression. Also, due to the larger size of the rabbit brain we expected to find differences in the onset times and patterning of the induced behaviors as a function of frontal and occipital cortical injection of KCI, which would point to critical cortical areas involved in the activation of the behaviors.
Rabbits
according to the scheme of Fig. 1, which shows idealized coordinates of the rabbit brain according to the atlas of Monnier and Gangloff [18]. F o u r injection cannula guides (20 ram long, internal diameter 0.6 Irma) were situated flush with the dura, over the frontal and occipital cortices. Two bipolar, teflon coated, silver, a.c. recording electrodes, 0.25 mm tip diameter, were placed into the dorsal hippocampi (with coordinates from bregma, 4 mm lateral, 4 nun posterior, and 7.5 m m inferior, perpendicular to the skull). Four glass capillary d.c. recording electrodes were placed 5-6 mm lateral from bregma into the frontal and posterior cortices (1 m m anterior and 12 m m posterior, respectively). The capillaries contained agar soaked with 20 % NaCI solution, and a chloridized silver spiral. A common Ag-AgCI screw electrode was placed about 13 m m anterior to bregma. These components were cemented to the skull with dental acrylic.
Procedure The rabbits were tested in transparent experimental boxes, that were 43 cm long, 28 cm wide, with 25 cm high wails, and totally open on top. The animals actually lived in these boxes, some throughout the whole experiment, and hence, were totally adapted to the experimental situation. They always had food available in the box, which consisted of whole carrots and/or solid Larsen pellets. Six per cent KCI solution was injected into the cortices via small eannula~ (dia. external 0.5 ram, internal 0.2 mm) by
METHOD
Animals and implantation Six rabbits, weighing between 2 and 3 kg, were anaesthetized with pentobarbitone and ether, and surgically prepared
xJPH was supported in part by a National Academy of Sciences-Czechoslovak Academy of Sciences exchange fellowship, and subsequently by a National Institute of Mental Health postdoctoral fellowship. Now at the Institute of Pharmacology, University of Ziirich, Gloriastrasse 32, Zfirich Switzerland. 2We thank Dr. Jan Bureg, in whose laboratory this work was done. 595
596
HUSTON AND BRO~EK
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An animal had to abstain from eating for at least 5 rain before a KCI injection was administered. In practice, the periods of zero eating that preceded KCI injections varied up to several hours, with typical intervals of from 20-40 rain between trials. Hence, at the time of each trial the rabbits were in a state of acute satiation. An animal was generally given no more than 5 trials per day of testing. The onset and duration of the monitored behavior of the animals was either marked on the EEG records with a handoperated event recorder, or, in most cases, registered by means of stop watches. During most experimental sessions only food was made available to the rabbit, hence, the data consisted mainly of eating behavior.
ZX
RESULTS
FIG. 1. Idealized rabbit brain according to Monnier and Gangloff [18], with positions of recording electrodes and injection cannulae. way of polyethylene tubing which extended from a microsyringe. The KCI was always applied unilaterally on any given trial. One ttl KCI was generally sufficient to trigger a wave of spreading depression, although at times up to 5 t~l were necessary. An eight channel polygraph was used for recording purposes. Cortical and hippocampal EEG and steady potential changes were recorded on only a portion of the trials, since the leads somewhat interfered with free head movement of the rabbits.
Of the six rabbits tested, it was possible to elicit eating by cortical spreading depression in 9 hemispheres of 5 rabbits. Figure 2 shows a portion of a recording taken during a single wave of spreading depression induced by injection of KCI into a frontal cortex. The top trace of each of the 3 rows indicates the time since injection (0 min) of KCI. The second trace (I-Hip) represents hippocampal EEG from the side ipsilateral to the depressed hemisphere. The third trace (C-Co) is the cortical EEG from the nondepressed contralateral hemisphere. The fourth trace represents the ipsilateral cortical steady potential change that accompanies the wave of spreading depression. It shows the peak negativity at the frontal electrode (upward excursion) to be about 5 mV at about 1.4 min after injection, and peak negativity at the posterior electrode (downward deflection) to occur about 3.6 min after injection. fmia
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FIG. 2. Polygraph recording of EEG and D-C potentials during a single wave of spreading depression induced by anterior cortical KCI injection. EEG was recorded from dorsal hippocampus ipsilateral to the depressed hemisphere (I-Hip), and from the nondepressed cortex (G-Co). I - D e represents the steady potential change recorded from the depressed cortex (an upward excursion is negativity at the frontal electrode; a downward deflection is negativity at the posterior pole). Note the onset of eating and correlated EEG changes at 2.4 rain after injection of KCI.
CSD AND CONSUMMATORY BEHAVIOR
597
Eating in this case, began about 2.5 min after injection of KCI (see row B) and lasted until 4 min after injection. Note the hippocampal synchronization (theta activity) that accompanies the onset and duration of eating behavior. The top histogram of Fig. 3 shows the distribution of onset times of 77 cases of eating induced by cortical spreading depression in 5 rabbits. Onset of eating was most probable (26 % of the time) between 4 and 6 min after injection of KCI. About 85 per cent of the elicited eating commenced within the first 8 min of the initiation of spreading depression. The bottom histogram of Fig. 3 represents the incidence of eating during the trials when eating was elicited by CSD. F o r example, in about 28 per cent of the positive trials some eating was observed to occur between 6 a n d 8 min after injection, the period of highest incidence of observed eating. The
incidence of eating was satisfactorily recorded only during 56 trials. The duration of the eating bouts ranged from a few bites to l0 min of continuous biting and chewing, with an overall mean of 2.2 min, and a range of means from 0.64 to 3.4 min for the 5 rabbits. These histograms represent the combined data for cortical spreading depression induced in the occipital and frontal cortices. Since we expected to find differences in the onset distributions of eating between frontal and occipital cortical injections, the data were redrawn according to Fig. 4, which shows the histograms of the onset distributions of eating induced by frontal (top) and occipital (bottom) injections. Unexpectedly, the onset distributions were very similar, with no significant difference between the rncans, 4.4 min vs. 5.3 rain respectively, for anterior and posterior injection. The incidence of elicited eating in those rabbits in which it could be demonstrated approximated 50 per cent of trials. During some sessions eating was elicited on 100 per cent of the
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FIG. 3. Top: histogram showing distribution of onset times of 77 cases of eating (,~ 50 per cent of trials) induced by cortical spreading depression in 5 rabbits. Zero min represents time of KC1 injection. Dotted line is the arithmetic mean. Bottom: histogram showing the incidence of observed eating throughout spreading depression in 56 trials.
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FIG. 4. Histograms of distributions of onset times of eating elicited by injection of KC1 into anterior (top) and posterior (bottom) cortices of 5 rabbits. Zero min represents time of KCI injection. Dotted lines indicate arithmetic means.
598
HUSTON AND BRO~.EK
trials. These estimates are biased, however, since, due to the metabolic and behavioral exhaustion that takes place with cumulative effects of CSD [6], a session was terminated when an animal failed to respond several times in succession. On about 25 per cent of the trials the KCI injections were apparently subthreshold and did not trigger a wave of spreading depression. On such occasions eating was observed to occur within 15 rain of the injection on 7 per cent of the trials. This indicates that the elicited eating on the successful trials was due principally to properties of the CSD rather than some other effect of the KCI injection. One animal, who was tested with water in the box, exhibited SD-induced drinking and/or eating. All cases of elicited eating were accompanied and often preceded by other signs of behavioral arousal, such as turning in a circle, raising the ears, orienting responses, and digging movements. Other behavior that was frequently observed during CSD was yawning and stretching.
DISCUSSION
The elicitation of eating, locomotion and orienting behavior in rabbits by single waves of CSD, and the occurrence of yawning responses, concur with the earlier data on rats [15, 16]. One important difference between the procedures used is that in the present study waves of CSD were administered by injecting KCI solution through implanted cannulae rather than by electrophoretic injection of K ÷ ions. This rules out an explanation of the induced behavior as an aftereffect of the current passed through the brain. A discrepancy between the results with rabbits and those with rats is the comparative flatness of the onset distribution of induced eating found in the present study when the data were averaged across rabbits. A possible explanation is the difference in behaviors required in the two situations. The rats had to perform relatively complex locomotor and orienting movements in order to eat or to lick at the water spout, whereas the rabbits merely required movement of the head to reach the food source. On the other hand, the somewhat flat distribution and failure to find differences in mean onset times between frontal and occipital injections suggests an explanation of the behavioral effects in terms of the general arousal reactions that accompany CSD. F o r example, single waves of CSD, triggered in one hemisphere of rats, are accompanied by
cortical arousal (EEG desynchronization) in the contralateral hemisphere [4, 28]. A variety of manipulations that presumably arouse the animal can facilitate operant responding [11], copulation [3, 7], as well as food and water intake [1, 22, 26] in rats. Arousal may account for the CSD-elicited behavior in tote, or at least in part. Relevant in this context is the hypothesis that displacement activities serve to decrease the level of arousal [9], andthe somewhat relatedconcept of adjunctive behavior, as espoused recently [12, 27] for displacement behaviors that occur under intense motivational conditions. An alternate hypothesis, proposed earlier [16], is that the effect reflects cortical-subcortical interactions and that the induced behavior is the result of activation of subcortical circuits involved in motivated behaviors that are modulated by cortical activity. This possibility can not be ruled out, especially since CSD has been shown to interact with hypothalamic mechanisms in a variety of ways, such as by attenuation of hypothalamic noradrenaline [10], EEG [29], evoked potentials [21], activity of single units [5], electrical selfstimulation [5, 20], and electrically elicited eating and drinking [14]; as well as by causing a relapse of hypothalamic lesioninduced aphagia after partial recovery [2, 25]. Subthreshold quantities of KCI that did not trigger CSD were seldom followed by eating. Elsewhere, both drinking and eating have been induced in goats by infusing larger amounts of hypertonic KCI solution into the 3rd ventricle [19]. Hence, it may be that in the present experiment a similar effect was occasioned by the increase in extracellular K + concentration accompanying the massive neuronal depolarization that precedes SD. Other sources support the conjecture that cortical spreading depression can energize certain behaviors. F o r example, Suzuki and Uneoka [24] noted "circus movements, exploratory behavior and alimentary behavior such as chewing and gnawing" during CSD in some rabbits. Bilateral cortical application of KCI has been shown to facilitate lordosis responses in female rats [8]. Unpublished data by Huston and Bureg suggests that striatal SD in chickens can elicit pecking of grain, and that caudate SD in rats energizes eating and drinking. Similarly, Stille and Sayers [23] have shown caudate SD to induce gnawing, licking and locomotor responses. Also the bursting of licking, wheel running and Sidman avoidance observed by Freedman [13], presumably during multiple waves of CSD induced by placing KCI solution onto the dura, may reflect the elicitation as well as recovery of the behaviors.
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