Journal of Comparative and Physiological Psychology 1975, Vol. 89, No. 7, 733-737
Ontogenetic Dissociation of Two Classes of Habituation John M. Williams Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School
Leonard W. Hamilton Rutgers—The State University
Peter L. Carlton Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School The rates of decrement of two classes of response (an elicited startle reflex and emitted exploratory behavior) were determined in rats of two different ages (15 and 36 days). The rate of decrement in the startle reflex was not clearly differentiated as a function of age. In contrast, there was no evidence of habituation of exploration in the younger animals, whereas the older rats uniformly showed profound response decrements. This ontogenetic dissociation of the two instances of response decrement indicates that accounts of both instances in terms of a common process called habituation may be unwarranted. In addition, these data, in conjunction with earlier findings, indirectly support the possibility that reflex decrements may be relatively more dependent on brain serotonin whereas decrements in exploration may be more dependent on normal cholinergic activity in brain.
In a recent paper (Williams, Hamilton, & Carlton, 1974) we presented data suggesting that two instances of response decrement usually taken as indexes of a common process of habituation could be pharmacologically dissociated. In particular, we found that the decrement of an elicited reflex (a startle response) was relatively unaffected by the anticholinergic drug scopolamine, whereas the decrement of an emitted response (exploratory behavior) was profoundly attenuated by this same drug. These data indicate, among other things, that the rather general tendency to attribute various instances of response decrement to a single hypothetical process called habituation (e.g., Carlton, 1969; Thompson, Groves, Teyler, & Roemer, 1973) embodies an implicit assumption about that process that is largely unwarranted. In this article, we explore this prospect in yet another way, This research was supported by Grant MH08585 to Peter L. Carlton and by Grant MH-16448 to Leonard W. Hamilton, both grants from the National Institute of Mental Health. Requests for reprints should be sent to Peter L. Carlton, Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, New Jersey 08854.
a way that derives from two other sets of earlier data. One of these is the report that another drug, parachlorophenylalanine (PCPA), does attenuate the rate of response decrement of the elicited startle response (Carlton & Advokat, 1973) and thus differs from scopolamine. The second of these derives from two reports indicating that sensitivities to these two drugs develop at different rates in the course of ontogenesis (Campbell, Lytle, & Fibiger, 1969; Mabry & Campbell, 1974). In the first of these studies it was found that the hypermotility induced by scopolamine could only be obtained at ages greater than 21 days, whereas in the second study, such hypermotility due to PCPA could be obtained from 15 days onward. Taken together, these data indicate the following: Decrement in the startle reflex is demonstrably sensitive to PCPA, whereas a second drug, scopolamine, has little effect on this instance of response decrement but does profoundly attenuate yet another instance of response decrement, exploration; sensitivity to PCPA appears at 15 days and thereafter, but sensitivity to scopolamine
733
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J. M. WILLIAMS, L. W. HAMILTON, AND P. L. CARLTON
appears only at 21 days and thereafter. Therefore, to the extent that the pharmacological dissociation of the two instances of response decrement may be supposed to indicate something about the physiological mechanisms underlying them, it might be expected that these same two instances of response decrement could be ontogenetically dissociated; that is, at 15 days of age, decrement in startle reflex might be expected to proceed normally (as suggested by the sensitivity to PCPA at that age), whereas decrement in exploration would not so proceed (as suggested by the lack of sensitivity to scopolamine at that age). In this sense, the fact of pharmacological dissociation may be said to generate the possibility of ontogenetic dissociation; it is this possibility that we examine here. METHOD Subjects The subjects were 31 Sprague-Dawley albino rats born of dams that were pregnant when obtained from the Carworth Co., New City, New York. The litters were housed separately in nesting cages until weaning at 20 days of age and then in littermate groups of two or three in standard suspended cages. All were housed under conditions of constant illumination, free access to the mother before weaning, and ad-lib food and water thereafter.
Apparatus The test chamber for startle response measurement consisted of a stainless steel box measuring 195 X 120 X 118 mm, with a hardware cloth lid; the chamber weighed 776 g. A ceramic phonograph cartridge was in contact with one side of the box, which rested on a marble balance table. The output from this cartridge was wired into a digital voltmeter which recorded the maximum voltage received during the .5-sec period initiated by a signal from associated programming equipment. These voltages were used to index response amplitude. This signal occurred every 40 sec and was accompanied by a mild puff of air from 10 jets located 14 cm above the floor of the chamber. The apparatus for measuring exploration consisted of a clear plastic cage and lid, with a hardware cloth floor. Centered on two opposite walls of the cage, 35 mm above the floor, were round openings which were 30 mm in diameter. These opened into tubes of the same diameter, 25 mm long, which were blocked at the end by clear plastic. The only illumination inside the chamber came from two dim red lights located 1 cm into
the tubes that served as photocell beams. When the rat interrupted either of these beams by inserting its head into the tube, this exploratory response was recorded by counters located in another room. The entire apparatus was housed in a sound-attenuating chamber. Procedure The subjects were divided randomly into two groups to be tested at different ages; each group consisted of pups from all five litters. The infant group (ft = 11) was tested when 15-16 days old; the adult group (n = 11) was tested when 36-39 days old. All animals were tested for habituation of exploratory and startle responding on consecutive days in counterbalanced order. On the day of testing, each animal was placed in the appropriate apparatus for a 1-hr session. In the test for exploratory habituation, the total number of entries into each tube was recorded for each of eight periods of 7.5-min duration. The startle-habituation scores were also totaled over approximately the same time interval (i.e., the sum of each 11 startle scores, startle stimuli being presented every 40 sec). Thus, each animal generated eight scores in each apparatus.
RESULTS The levels of responding in the first periods were, for both exploration and startle, lower in the infants than in the adults. (The respective means were 9.8 and 30.9 responses in the exploratory situation and 56.2 and 105.6 in the startle situation; the means of both startle amplitude and of exploratory responses reliably differ, p < .002 by twotailed Mann-Whitney U test in both instances.) These differences are almost certainly artifactual ones due to, first, the fact that the infants weighed less in the case of startle and, second, a relatively greater difficulty in response emission, given the physical characteristics of the apparatus for assessing exploration. As noted in Method, 6 of the 11 animals in each group were first given startle stimuli and were subsequently studied in the exploratory apparatus; the remaining 5 were given the opposite order of treatments. The possibility of order effects was evaluated by comparing each group (infant or adult) in terms of both measures as a function of which treatment had been given first. There was no consistent evidence of any order effect. The averaged numbers of exploratory
ONTOGENETIC DISSOCIATION OF HABITUATION
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FIGURE 1. Mean exploratory responses (left panel) and mean startle response amplitudes indexed as arbitrary voltage units (right panel) as a function of successive periods of the experimental session.
responses in each period for all animals in cordingly, it would appear that aside from each group are plotted in the left panel of the differences in initial values in Period 1 Figure 1. Every adult emitted fewer re- noted above, the decrement in startle amplisponses in Period 8 than in Period 1 (p < tude does not vary as a function of age in .01 by two-tailed Wilcoxon's T test). In the same way that decrement in exploratory contrast, there was no statistically reliable responding obviously does. difference between these periods among the DISCUSSION infants; four infants emitted fewer responses in Period 8 than in Period 1, five emitted The fact that response decrement in an more, and two showed no change (all non- exploratory situation varies with age replizero differences were small). Thus, habitua- cates data reported by Bronstein, Neiman, tion of exploration occurs in the adult but Wolkoff, and Levine (1974) in an article not in the infant. Furthermore, the infants that appeared while the present one was in actually emitted more responses in Period preparation. In addition, the data reported 8 than did the adults. This difference al- here indicate that although one instance of though small was a reliable one (p < .02 by response decrement (exploration) was ontotwo-tailed Mann-Whitney U test). genetically dissociated, a second (startle) The averaged amplitudes of startle (in was not. This fact has at least two general arbitrary voltage units) arc shown in the implications. right panel of Figure 1. Both infants and The first of these is that normal reflexive adults showed reliable reflex decrements be- behavior evidently develops earlier than does tween Periods 1 and 8 (p < .001 by two- the more complex behavior involved in extailed Wilcoxon's T test). The startle ampli- ploration, presumably emitted rather than tudes of both groups tended to level off at a reflexive responses of the animal; by "norminimum amplitude of about thirty units. mal" we mean, in this context, not only the The decline in amplitudes that occurred occurrence of the behavior itself but its before either group had reached this level decrement as well. Thus, those complex (i.e., during Periods 1, 2, and 3) was essen- processes that modulate the totality of retially identical for both adults and infants. flexive behavior appear to be intact at an In particular, decrements in amplitude from earlier age than those apparently more comPeriod 1 to Period 2 and from Period 2 to plex, operant behaviors involving processes Period 3 for the adults were 5.4 and 11.8, like "orienting" and their decrement. respectively; the corresponding decrements The second implication of these data is for the infants were 5.5 and 12.2, respec- essentially an elaboration of a point pretively. Thus, in the range within which dec- viously made on pharamcological grounds: rement could occur in both groups, the ex- Instances of response decrement viewed as tent of those decrements was the same. Ac- reflecting a common process called habitua-
736
J. M. WILLIAMS, L. W. HAMILTON, AND P. L. CAHLTON
tion cannot reasonably be viewed as having, in fact, such commonality, not only on pharmacological grounds but on ontogenetic ones as well. Yet another aspect of these data, in addition to the foregoing, has to do with the substrates that may underlie both the pharmacological and ontogenetic dissociations described here. The effects of PCPA on decrements in reflexive behavior can, with reasonable certainty, be ascribed to the depletion of brain serotonin (5-HT) that this drug engenders; the effects of the anticholinergic scopolamine can, with less certainty, be ascribed to an interference with the normal actions of brain acetylcholine (ACH). If these suppositions about substrates are granted, then four different lines of evidence cohere in the suggestion that decrements in reflexive behavior may be relatively more dependent on the activity of 5-HT whereas decrements in emitted behavior may be more dependent on the activity of ACH. The first of these lines of evidence is the previously cited fact that reflex decrements are attenuated by PCPA but not by scopolamine, although the latter drug has profound effects on the normal decrement in exploratory behavior. These data iiiferentially imply a greater dependency of the reflex decrement on 5-HT than on ACH; the exploratory decrement may be relatively more dependent on ACH than on 5-HT, perhaps in the way suggested by Swonger and Rech (1972). The second line of evidence, closely related to the first, is the previously described ontogenetic differences in sensitivity to PCPA and scopolamine; this differentiation with age implies a differentiation in the activity of the relevant substrate. The third line of evidence combines the first two in the sense that on the basis of these inferences about substrate, different instances of response decrement (reflex vs. operant) should differ in ontogeny. That, of course, is the import of the data reported here. The fourth line of evidence is to be found in the previous article by Williams et al. (1974). In addition to the differential effects of scopolamine on two instances of response
decrement reported there, we also reported that lesions restricted to the medial septum attenuated both reflex and exploratory decrements. Because of the variety of findings implicating ACH in limbic forebrain function (Campbell et al., 1969; Carlton, 1969; Feigley & Hamilton, 1971; Hamilton & Grossman, 1969), the finding that medial septal lesions, like scopolamine, attenuated the decrement in exploration was not unexpected. However, that such lesions, unlike scopolamine, also attentuated reflex decrements was an unanticipated result that may, in light of the relevant histochemistry (cf. Ungerstedt, 1971), be due to a diffuse depletion of 5-HT analogous to that found after much more massive lesions of the septum (Lints & Harvey, 1969). Thus, the lesion may have disrupted the activities of both 5-HT and ACH so as to produce both of the effects seen separately after separate pharmacological disruptions of the activity of these brain amines. Thus, pharmacological, ontogenetic, and anatomical sets of data apparently converge in suggesting that different instances of response decrement are differentially dependent on different biochemical substrates. However, the definitive examination of this possibility will require correlative biochemical data obtained in parallel with the behavioral data. REFERENCES Bronstein, P. M., Neiman, H., Wolkoff, F. D., & Levine, M. J. The development of habituation in the rat. Animal Learning and Behavior, 1974, 8, 92-96. Campbell, B. A., Lytle, L. D., & Fibiger, H. C. Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science, 1969, 166, 635-637. Carlton, P. L. Brain-acetylcholine and inhibition. In J. T. Tapp (Ed.), Reinforcement and behavior. New York: Academic Press, 1969. Carlton, P. L., & Advokat, C. Attenuated habituation due to parachlorophenylalanine. Pharmacology Biochemistry and Behavior, 1973, 1, 657-663. Feigley, D. A., & Hamilton, L. W. Response to novel environment following septal lesions or cholinergic blockade in rats. Journal of Comparative and Physiological Psychology, 1971, 76, 496-504. Hamilton, L. W., & Grossman, S. P. Behavioral changes following disruption of central choliner-
ONTOGENETIC DISSOCIATION OF HABITUATION gic pathways. Journal of Comparative and Physiological Psychology, 1969, 69, 76-82. Lints, C. E., & Harvey, J. A. Altered sensitivity to footshook and decreased content of serotonin following brain lesions in the rat. Physiology and Behavior, 1969, 67, 23-32. Mabry, P. D., & Campbell, B. A. Ontogeny of serotonergic inhibition of behavioral arousal in the rat. Journal of Comparative and Physiological Psychology, 1974, 86, 193-201. Swonger, A. K., & Reoh, 11. H. Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a Y-maze. Journal of Comparative and Physiological Psychology, 1972, 81, 509-522.
737
Thompson, R. F., Groves, P. M., Teyler, T. J., & lloemer, R. A. A dual-process theory of habituation: Theory and behavior. In H. V. S. Peeke & M. J. Herz (Eds.), Habituation (Vol. 1). New York: Academic Press, 1973. Ungerstedt, U. Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiologica Scandinavica, 1971, 82, 1-48. Williams, J. M. Hamilton, L. W., & Carlton, P. L. Pharmacological and anatomical dissociation of two types of habituation. Journal of Comparative and Physiological Psychology, 1974, 87, 724732. (Received September 12, 1974)
Ontogenetic Dissociation of Two Classes of Habituation John M. Williams Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School
Leonard W. Hamilton Rutgers—The State University
Peter L. Carlton Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School The rates of decrement of two classes of response (an elicited startle reflex and emitted exploratory behavior) were determined in rats of two different ages (15 and 36 days). The rate of decrement in the startle reflex was not clearly differentiated as a function of age. In contrast, there was no evidence of habituation of exploration in the younger animals, whereas the older rats uniformly showed profound response decrements. This ontogenetic dissociation of the two instances of response decrement indicates that accounts of both instances in terms of a common process called habituation may be unwarranted. In addition, these data, in conjunction with earlier findings, indirectly support the possibility that reflex decrements may be relatively more dependent on brain serotonin whereas decrements in exploration may be more dependent on normal cholinergic activity in brain.
In a recent paper (Williams, Hamilton, & Carlton, 1974) we presented data suggesting that two instances of response decrement usually taken as indexes of a common process of habituation could be pharmacologically dissociated. In particular, we found that the decrement of an elicited reflex (a startle response) was relatively unaffected by the anticholinergic drug scopolamine, whereas the decrement of an emitted response (exploratory behavior) was profoundly attenuated by this same drug. These data indicate, among other things, that the rather general tendency to attribute various instances of response decrement to a single hypothetical process called habituation (e.g., Carlton, 1969; Thompson, Groves, Teyler, & Roemer, 1973) embodies an implicit assumption about that process that is largely unwarranted. In this article, we explore this prospect in yet another way, This research was supported by Grant MH08585 to Peter L. Carlton and by Grant MH-16448 to Leonard W. Hamilton, both grants from the National Institute of Mental Health. Requests for reprints should be sent to Peter L. Carlton, Department of Psychiatry, College of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, New Jersey 08854.
a way that derives from two other sets of earlier data. One of these is the report that another drug, parachlorophenylalanine (PCPA), does attenuate the rate of response decrement of the elicited startle response (Carlton & Advokat, 1973) and thus differs from scopolamine. The second of these derives from two reports indicating that sensitivities to these two drugs develop at different rates in the course of ontogenesis (Campbell, Lytle, & Fibiger, 1969; Mabry & Campbell, 1974). In the first of these studies it was found that the hypermotility induced by scopolamine could only be obtained at ages greater than 21 days, whereas in the second study, such hypermotility due to PCPA could be obtained from 15 days onward. Taken together, these data indicate the following: Decrement in the startle reflex is demonstrably sensitive to PCPA, whereas a second drug, scopolamine, has little effect on this instance of response decrement but does profoundly attenuate yet another instance of response decrement, exploration; sensitivity to PCPA appears at 15 days and thereafter, but sensitivity to scopolamine
733
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J. M. WILLIAMS, L. W. HAMILTON, AND P. L. CARLTON
appears only at 21 days and thereafter. Therefore, to the extent that the pharmacological dissociation of the two instances of response decrement may be supposed to indicate something about the physiological mechanisms underlying them, it might be expected that these same two instances of response decrement could be ontogenetically dissociated; that is, at 15 days of age, decrement in startle reflex might be expected to proceed normally (as suggested by the sensitivity to PCPA at that age), whereas decrement in exploration would not so proceed (as suggested by the lack of sensitivity to scopolamine at that age). In this sense, the fact of pharmacological dissociation may be said to generate the possibility of ontogenetic dissociation; it is this possibility that we examine here. METHOD Subjects The subjects were 31 Sprague-Dawley albino rats born of dams that were pregnant when obtained from the Carworth Co., New City, New York. The litters were housed separately in nesting cages until weaning at 20 days of age and then in littermate groups of two or three in standard suspended cages. All were housed under conditions of constant illumination, free access to the mother before weaning, and ad-lib food and water thereafter.
Apparatus The test chamber for startle response measurement consisted of a stainless steel box measuring 195 X 120 X 118 mm, with a hardware cloth lid; the chamber weighed 776 g. A ceramic phonograph cartridge was in contact with one side of the box, which rested on a marble balance table. The output from this cartridge was wired into a digital voltmeter which recorded the maximum voltage received during the .5-sec period initiated by a signal from associated programming equipment. These voltages were used to index response amplitude. This signal occurred every 40 sec and was accompanied by a mild puff of air from 10 jets located 14 cm above the floor of the chamber. The apparatus for measuring exploration consisted of a clear plastic cage and lid, with a hardware cloth floor. Centered on two opposite walls of the cage, 35 mm above the floor, were round openings which were 30 mm in diameter. These opened into tubes of the same diameter, 25 mm long, which were blocked at the end by clear plastic. The only illumination inside the chamber came from two dim red lights located 1 cm into
the tubes that served as photocell beams. When the rat interrupted either of these beams by inserting its head into the tube, this exploratory response was recorded by counters located in another room. The entire apparatus was housed in a sound-attenuating chamber. Procedure The subjects were divided randomly into two groups to be tested at different ages; each group consisted of pups from all five litters. The infant group (ft = 11) was tested when 15-16 days old; the adult group (n = 11) was tested when 36-39 days old. All animals were tested for habituation of exploratory and startle responding on consecutive days in counterbalanced order. On the day of testing, each animal was placed in the appropriate apparatus for a 1-hr session. In the test for exploratory habituation, the total number of entries into each tube was recorded for each of eight periods of 7.5-min duration. The startle-habituation scores were also totaled over approximately the same time interval (i.e., the sum of each 11 startle scores, startle stimuli being presented every 40 sec). Thus, each animal generated eight scores in each apparatus.
RESULTS The levels of responding in the first periods were, for both exploration and startle, lower in the infants than in the adults. (The respective means were 9.8 and 30.9 responses in the exploratory situation and 56.2 and 105.6 in the startle situation; the means of both startle amplitude and of exploratory responses reliably differ, p < .002 by twotailed Mann-Whitney U test in both instances.) These differences are almost certainly artifactual ones due to, first, the fact that the infants weighed less in the case of startle and, second, a relatively greater difficulty in response emission, given the physical characteristics of the apparatus for assessing exploration. As noted in Method, 6 of the 11 animals in each group were first given startle stimuli and were subsequently studied in the exploratory apparatus; the remaining 5 were given the opposite order of treatments. The possibility of order effects was evaluated by comparing each group (infant or adult) in terms of both measures as a function of which treatment had been given first. There was no consistent evidence of any order effect. The averaged numbers of exploratory
ONTOGENETIC DISSOCIATION OF HABITUATION
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FIGURE 1. Mean exploratory responses (left panel) and mean startle response amplitudes indexed as arbitrary voltage units (right panel) as a function of successive periods of the experimental session.
responses in each period for all animals in cordingly, it would appear that aside from each group are plotted in the left panel of the differences in initial values in Period 1 Figure 1. Every adult emitted fewer re- noted above, the decrement in startle amplisponses in Period 8 than in Period 1 (p < tude does not vary as a function of age in .01 by two-tailed Wilcoxon's T test). In the same way that decrement in exploratory contrast, there was no statistically reliable responding obviously does. difference between these periods among the DISCUSSION infants; four infants emitted fewer responses in Period 8 than in Period 1, five emitted The fact that response decrement in an more, and two showed no change (all non- exploratory situation varies with age replizero differences were small). Thus, habitua- cates data reported by Bronstein, Neiman, tion of exploration occurs in the adult but Wolkoff, and Levine (1974) in an article not in the infant. Furthermore, the infants that appeared while the present one was in actually emitted more responses in Period preparation. In addition, the data reported 8 than did the adults. This difference al- here indicate that although one instance of though small was a reliable one (p < .02 by response decrement (exploration) was ontotwo-tailed Mann-Whitney U test). genetically dissociated, a second (startle) The averaged amplitudes of startle (in was not. This fact has at least two general arbitrary voltage units) arc shown in the implications. right panel of Figure 1. Both infants and The first of these is that normal reflexive adults showed reliable reflex decrements be- behavior evidently develops earlier than does tween Periods 1 and 8 (p < .001 by two- the more complex behavior involved in extailed Wilcoxon's T test). The startle ampli- ploration, presumably emitted rather than tudes of both groups tended to level off at a reflexive responses of the animal; by "norminimum amplitude of about thirty units. mal" we mean, in this context, not only the The decline in amplitudes that occurred occurrence of the behavior itself but its before either group had reached this level decrement as well. Thus, those complex (i.e., during Periods 1, 2, and 3) was essen- processes that modulate the totality of retially identical for both adults and infants. flexive behavior appear to be intact at an In particular, decrements in amplitude from earlier age than those apparently more comPeriod 1 to Period 2 and from Period 2 to plex, operant behaviors involving processes Period 3 for the adults were 5.4 and 11.8, like "orienting" and their decrement. respectively; the corresponding decrements The second implication of these data is for the infants were 5.5 and 12.2, respec- essentially an elaboration of a point pretively. Thus, in the range within which dec- viously made on pharamcological grounds: rement could occur in both groups, the ex- Instances of response decrement viewed as tent of those decrements was the same. Ac- reflecting a common process called habitua-
736
J. M. WILLIAMS, L. W. HAMILTON, AND P. L. CAHLTON
tion cannot reasonably be viewed as having, in fact, such commonality, not only on pharmacological grounds but on ontogenetic ones as well. Yet another aspect of these data, in addition to the foregoing, has to do with the substrates that may underlie both the pharmacological and ontogenetic dissociations described here. The effects of PCPA on decrements in reflexive behavior can, with reasonable certainty, be ascribed to the depletion of brain serotonin (5-HT) that this drug engenders; the effects of the anticholinergic scopolamine can, with less certainty, be ascribed to an interference with the normal actions of brain acetylcholine (ACH). If these suppositions about substrates are granted, then four different lines of evidence cohere in the suggestion that decrements in reflexive behavior may be relatively more dependent on the activity of 5-HT whereas decrements in emitted behavior may be more dependent on the activity of ACH. The first of these lines of evidence is the previously cited fact that reflex decrements are attenuated by PCPA but not by scopolamine, although the latter drug has profound effects on the normal decrement in exploratory behavior. These data iiiferentially imply a greater dependency of the reflex decrement on 5-HT than on ACH; the exploratory decrement may be relatively more dependent on ACH than on 5-HT, perhaps in the way suggested by Swonger and Rech (1972). The second line of evidence, closely related to the first, is the previously described ontogenetic differences in sensitivity to PCPA and scopolamine; this differentiation with age implies a differentiation in the activity of the relevant substrate. The third line of evidence combines the first two in the sense that on the basis of these inferences about substrate, different instances of response decrement (reflex vs. operant) should differ in ontogeny. That, of course, is the import of the data reported here. The fourth line of evidence is to be found in the previous article by Williams et al. (1974). In addition to the differential effects of scopolamine on two instances of response
decrement reported there, we also reported that lesions restricted to the medial septum attenuated both reflex and exploratory decrements. Because of the variety of findings implicating ACH in limbic forebrain function (Campbell et al., 1969; Carlton, 1969; Feigley & Hamilton, 1971; Hamilton & Grossman, 1969), the finding that medial septal lesions, like scopolamine, attenuated the decrement in exploration was not unexpected. However, that such lesions, unlike scopolamine, also attentuated reflex decrements was an unanticipated result that may, in light of the relevant histochemistry (cf. Ungerstedt, 1971), be due to a diffuse depletion of 5-HT analogous to that found after much more massive lesions of the septum (Lints & Harvey, 1969). Thus, the lesion may have disrupted the activities of both 5-HT and ACH so as to produce both of the effects seen separately after separate pharmacological disruptions of the activity of these brain amines. Thus, pharmacological, ontogenetic, and anatomical sets of data apparently converge in suggesting that different instances of response decrement are differentially dependent on different biochemical substrates. However, the definitive examination of this possibility will require correlative biochemical data obtained in parallel with the behavioral data. REFERENCES Bronstein, P. M., Neiman, H., Wolkoff, F. D., & Levine, M. J. The development of habituation in the rat. Animal Learning and Behavior, 1974, 8, 92-96. Campbell, B. A., Lytle, L. D., & Fibiger, H. C. Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science, 1969, 166, 635-637. Carlton, P. L. Brain-acetylcholine and inhibition. In J. T. Tapp (Ed.), Reinforcement and behavior. New York: Academic Press, 1969. Carlton, P. L., & Advokat, C. Attenuated habituation due to parachlorophenylalanine. Pharmacology Biochemistry and Behavior, 1973, 1, 657-663. Feigley, D. A., & Hamilton, L. W. Response to novel environment following septal lesions or cholinergic blockade in rats. Journal of Comparative and Physiological Psychology, 1971, 76, 496-504. Hamilton, L. W., & Grossman, S. P. Behavioral changes following disruption of central choliner-
ONTOGENETIC DISSOCIATION OF HABITUATION gic pathways. Journal of Comparative and Physiological Psychology, 1969, 69, 76-82. Lints, C. E., & Harvey, J. A. Altered sensitivity to footshook and decreased content of serotonin following brain lesions in the rat. Physiology and Behavior, 1969, 67, 23-32. Mabry, P. D., & Campbell, B. A. Ontogeny of serotonergic inhibition of behavioral arousal in the rat. Journal of Comparative and Physiological Psychology, 1974, 86, 193-201. Swonger, A. K., & Reoh, 11. H. Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a Y-maze. Journal of Comparative and Physiological Psychology, 1972, 81, 509-522.
737
Thompson, R. F., Groves, P. M., Teyler, T. J., & lloemer, R. A. A dual-process theory of habituation: Theory and behavior. In H. V. S. Peeke & M. J. Herz (Eds.), Habituation (Vol. 1). New York: Academic Press, 1973. Ungerstedt, U. Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiologica Scandinavica, 1971, 82, 1-48. Williams, J. M. Hamilton, L. W., & Carlton, P. L. Pharmacological and anatomical dissociation of two types of habituation. Journal of Comparative and Physiological Psychology, 1974, 87, 724732. (Received September 12, 1974)
