Neuroendocrinology 18: 154-160 (1975)
Effects of Differential Hippocampal Damage upon Rhythmic and Stress-Induced Corticosterone Secretion in the Rat L inda P atia Lanier, C arol Van H artesveldt1, Bonita J. W eis and R. L. Isaacson1 University of Florida, Gainesville, Fla.
Key Words. Hippocampus • Stress • Diurnal corticosterone Abstract. The effects of dorsal, ventral, and near-total hippocampal lesions upon both rhythmic and stress-induced corticosterone secretion in adult male rats were examined. All hippocampally-damaged, cortically-damaged, and intact rats showed rhythmic corti costerone secretion as measured in 4 blood samples for each animal taken at 6-h intervals at least 1 week apart. There were no significant differences among the groups. In addition, there were no significant differences in the amount of stress-induced corticosterone across experimental groups.
The hippocampus has been implicated in the regulation of the hypo thalamic-hypophyseal-adrenocortical system by the results of experiments involving electrical stimulation of the hippocampus, corticosteroid implants in the hippocampus, and lesions of the hippocampus. However, several recent studies have indicated that near-total ablation of the hippocampus in the rat results in no significant changes in corticosterone either at various points in the diurnal cycle or in response to several stressful stimuli [Coover et al., 1971; W ilson and C ritchlow , 1973/74; K earley et al., 1974], Since manip ulations of small regions of the hippocampus by stimulation, hormone im plants, or electrolytic lesions alter adrenocortical secretion while destruction of most of the structure does not, it is possible that the hippocampus is regionally organized with respect to excitatory and inhibitory regulatory in fluences on the hypothalamic-hypophyseal-adrenocortical system. Inactiva-
Received: February 3rd, 1975; revised MS accepted: April 26th, 1975.
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1 This research was supported in part by grant NIH-MH-22199-01 to C.V.H., and grant NIH-M H-16384-04 to R.L.I.
Lanier/V an H artesveldt/W eis,'Isaacson
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tion of a localized portion of the hippocampus might lead to an imbalance between these regulatory control mechanisms which could be reflected in altered corticosterone production, whereas the inactivation of the entire structure might result in only a temporary functional disturbance of the system. Evidence indicates that the dorsal and ventral hippocampus are dif ferentiated with respect to neuroanatomical innervation and projections [Siegel and T assoni, 1971a, b], behavioral effects of lesions [E llen et al., 1964; H addad and R abe, 1967; L anier and Isaacson, 1975], and responses to implanted corticosteroid hormones [Bohus et al., 1968]. In this study the hypothesis that selective damage to the dorsal or ventral hippocampus might have different effects than large, near-total destruction of the hippocampus on diurnal and/or stress-induced corticosterone secretion was examined.
Subjects. 55 Long-Evans hooded rats of approximately 500 g at the beginning of the blood-sampling procedure were used. Most animals were previously used in a study examining the effects of differential hippocampal lesions on open field activity and response to amphetamine in the open field [Lanier and Isaacson, 1975]. At least 1 month inter vened between the end of the previous testing and the habituation phase of the present study. Blood sampling began 2-3 months postoperatively. Operative procedure. Clean surgical technique was used. All rats were anesthetized with Nembutal and given 55,000 units Bicillin preoperatively. The lesions were made by aspira tion with a 22-gauge blunt-tipped needle following essentially the same surgical procedures as Isaacson et al. [1961]. In the dorsal hippocampal group (DH), medial-dorsal cortex and the antero-dorsal portion of the hippocampus were removed. More lateral and caudal cortical lesions were made in the ventral hippocampal group (VH) so that ventral hippo campus could be exposed and removed. By combining these two methods, near-total hippocampal (H) lesions were made. In the cortical control group (CC), medial-dorsal and caudal-lateral cortex were removed, exposing the hippocampus but not damaging it. The skull was exposed and drilled but the dura was not damaged in the sham control group (SC). Sampling procedure. At the beginning of the habituation phase of the present study the animals were placed in a private colony room maintained on a 12-12 h light-dark cycle with the light portion of the cycle beginning at 08.00 h. All animals were given at least 2 weeks' adaptation to this colony room before any blood samples were taken. A within-subjects design was used. Each animal was sampled at 07.00, 13.00, 19.00, and 01.00 h for the diurnal cycle determination. At least 1 week intervened between successive blood-sampling sessions for any animal. Data from animals that died during the course of the experiment were excluded from data analysis. For at least 12 h prior to a blood-sampling session no one was admitted to the colony room. Animals were not replaced in the colony room until all animals in that sampling period had been removed and sampled. No more than 7 animals were sampled during a
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Materials and Methods
156
Lanier/V an H artesveldt/W eis/I saacson
Fig. 1. Reconstructions of the minimum (dark, stippled area) and maximum (crosshatched area) lesion extent for each of the brain-damaged groups. Row A illustrates the extent of damage for rats with large hippocampal lesions (Group H); row B illustrates the damage to animals with ventral hippocampal lesions (Group VH); row C illustrates the damage to animals with dorsal hippocampal lesions (Group DH); and row D illustrates the damage to the group of animals sustaining only neocortical damage (Group CQ .
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single 30-45 min sampling period. Each animal was individually removed from the colony room in his home cage and quickly placed in an ether jar. Blood samples of 1.5-2.2 cm3 were taken via intracardiac puncture within 2 min. Blood samples were centrifuged; the serum fraction was then aspirated and frozen for later fluorometric assay for corticosterone. The stress-sampling procedure was begun 1 week or more after the last diurnal cycle sample was taken. The stress-sampling period began at 08.00 h and lasted 45-60 min. Each animal was removed from the colony room, etherized and subjected to intracardiac puncture within a 2-min period but no blood sample was drawn. Each animal was then placed in his home cage in the sampling room and re-etherized 15 min later. Blood samples were then taken within 2 min after initiation of this second etherization. Assay procedure. Plasma corticosterone was measured fluorometrically following the basic procedure of Silber el at. [1958], All samples were assayed in triplicate. Assays were repeated in duplicate or triplicate when a lack of consistency was found over the samples or when samples were inadvertently lost during the assay procedure.
Differential Hippocampal Damage and Corticosterone Secretion
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Histology. Rats were given injections of an overdose of Nembutal and intracardially perfused consecutively with physiological saline and a 10% formalin solution. The brains were removed, embedded in celloidin and cut coronally at 30 ft. Every eighth section was mounted and stained with thionin. The slides were examined and the extent of damage was drawn onto serial brain section diagrams. Rats were discarded from the study if they sustained moderate damage outside the target areas.
Results
Corticosterone Assay Five separate Kruskal-Wallis one-way analyses of variance on the data across the experimental groups at each of the time periods and with the stress sampling revealed no significant differences between groups at any of these sampling periods (see fig. 2, 3). Friedman two-way analyses of variance on the data within each group across the 4 time periods were found to be significant for each of the groups (DH : x2 = 10.62, df = 3, p < 0.02; VH : x2 = 9.96, df = 3, p < 0.02; H : x2 = 13.20, df = 3, p < 0.01; CC : x2 = 13.80, df = 3, p < 0.01; S C : x* = 12.09, df = 3, p< 0.01). A posteriori sign tests determined that the 7 p.m. (19.00 h) values for all groups were significantly greater than the 7 a.m. (07.00 h) and 1 p.m. (13.00 h) values (in these and all subsequent sign tests p < 0 .0 5 was considered to be significant). In addition, in all groups but the SC group the 1 a.m. (01.00 h) values were found to be significantly lower than the 7 p.m. (19.00 h) values. In the CC group the 7 a.m. (07.00 h) values were found to be significantly greater than the 1 p.m. (13.00 h) values. No other of these within-group comparisons was significant. Using sign tests, stress values were compared to the 7 a.m. (07.00 h) control values for each group. These tests revealed that all groups showed a significant increase in corticosterone levels after the stress.
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Histology Data from animals that sustained substantial bilateral damage to the thalamus and/or habenular complex were discarded from the study, as were animals who did not sustain significant bilateral damage to the hippocampal areas in question. The final ‘N’s for each group were: DH-5; VH-5; H-6; CC-8; SC-7. Figure 1 shows the maximum and minimum extent of damage for each of the 4 brain-damaged groups. For a more complete analysis of the damage sustained in each of the hippocampally-damaged groups see Lanier and Isaacson [1975].
158
L anier/V an H artesveldt/W eis/Isaacson
I I
07.00 h 13.00 h
□ 19.00 h 1 01.00 h
Fig. 3. Resting and ether stress levels of plasma corticosterone. Bars indicate group means; vertical lines indicate one standard error of the mean.
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Fig. 2. Resting levels of plasma corticosterone obtained at four 6-h intervals. Bars indicate group means; vertical lines indicate one standard error of the mean.
Differential Hippocampal Damage and Corticosterone Secretion
159
Discussion The hypothesis that the hippocampus might be organized in a dorsalventral dimension with respect to modulation of pituitary-adrenocortical activity was not supported by the results of the present experiment. Neither the rats with selective lesions nor those rats with more complete hippocampal destruction showed any alteration in the circadian rhythm of corticosterone secretion or in stress-induced corticosterone release. The present results are thus consistent with previous work showing that large, near-total hippo campal lesions have no effect on trough levels [Coover et al., 1971; K earley et al., 1974] or diurnal levels of corticosterone [Wilson and C ritchlow , 1973/74]. Furthermore, our results show that the dorsal and ventral hippo campus are not the locus of the hypothesized regional localization of control mechanisms of corticosterone secretion within the hippocampus. Thus, the lack of effects with large hippocampal lesions does not appear to be due to a masking produced by destruction of opposing modulatory centers in dorsal or ventral hippocampus. Similarly, J ackson and R egestein [1974] have shown that neither anterior, nor posterior, nor near-total ablation of the hippo campus in rhesus monkey affects diurnal cortisol secretion. The failure of either large or small hippocampal lesions to affect corti costerone secretion under either resting or stressful conditions must lead to a reconsideration of the generally accepted interpretation that the hippocampus inhibits pituitary-adrenocortical secretion. This interpretation was based primarily on studies showing that electrical stimulation of the hippocampus suppressed stress-induced increases in corticosteroids [e.g., M ason, 1958; Endr Qczi et al., 1959; K awakami et al., 1968], The discrepancies in the interpretations of electrical stimulation and ablation experiments emphasize the problems in generalizing from the results of experiments employing any particular technique, since each technique has its limitations. At present, it is not possible to construct a theory of the role of the hippocampus in the control of this hormone system which is consistent with the results of experiments using different experimental techniques. References Bohus , B.; N yakas, Cs ., and L issak, K.: Involvement of suprahypothalamic structures in
the hormonal feedback action of corticosteroids. Acta physiol, hung. 34: 1-8 (1968). tion of a lever-press response in hippocampectomized animals. Physiol. Behav. 7; 727732 (1971).
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Coover, G. D .; G oldman, L., and L evine, S.: Plasma corticosterone levels during extinc
L anier/V an H artesveldt/W eis/Isaacson
160
E llen, P.; W ilson, A.S., and Powell , E .W .: Septal inhibition and timing behavior in
the rat. Expl. Neurol. 10: 120-132 (1964). E ndroczi, E.; L issak, K .; Bohus, B., and K ovacs, S .: The inhibitory influence of archi-
cortical structures on pituitary-adrenal function. Acta physiol, hung. 16: 17-22 (1959). H addad, R. K. and R abe, A .: Effect of selective hippocampal lesions in the rat on DRL-20
acquisition. J. Psychol. Studies 15: 106-124 (1967). Isaacson, R.L.; D ouglas, R.J., and M oore, R.Y.: The effect of radical hippocampal
ablation on acquisition of an avoidance response. J.cornp. physiol. Psychol. 54: 625628 (1961). J ackson, W .J. and R egestein, Q .R .: Hippocampectomy in rhesus monkeys: effects on plasma cortisol during two stressful conditions. 4th Annu. Soc. Neurosci. Meeting, St.Louis, Missouri (1974). K awakami, M .; S eto, K .; T erasawa, E .; Yoshida, K .; M iyamoto, T .; Sekiguchi, M., and H attori, Y .: Influence of electrical stimulation and lesion in limbic structure upon
biosynthesis of adrenocorticoid in the rabbit. Neuroendocrinology 3: 337-348 (1968). K earley, R.C.; Van H artesveldt, C., and W oodruff, M .L.: Behavioral and hormonal
effects of hippocampal lesions on male and female rats. Physiol. Psychol. 2: 187-196 (1974). L anier, L.P. and Isaacson, R.L.: Activity changes related to the location of lesions in the hippocampus. Behav. Biol. 13: 59-69 (1975). M ason, J.W .: The central nervous system regulation of ACTH secretion; in J asper, P roctor, K nighton , N oshay and Costello Reticular formation of the brain, pp. 645662 (Little Brown, Boston 1958). Siegel, A. and T assoni, J. P .: Differential efferent projections from the ventral and dorsal hippocampus of the cat. Brain Behav. Evol. 4: 185-200 (1971a). Siegel, A. and T assoni, J.P .: Differential efferent projections of the lateral and medial septal nucleus to the hippocampus in the cat. Brain Behav. Evol. 4: 201-219 (1971b). Silber, R .H .; Busch, R.D., and O slapas, R.: Practical procedure for elimination of corticosterone or hydrocortisone. Clin. Chem. 4: 278-285 (1958). W ilson, M. and C ritchi.ow , V.: Effect of fornix transection or hippocampectomy on rhythmic pituitary-adrenal function in the rat. Neuroendocrinology 13:29-40 (1973/74).
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:20:34 PM
Linda L anier, Box 97, Psychology Department, University of Florida, Gainesville, FL
32611 (USA)
Effects of Differential Hippocampal Damage upon Rhythmic and Stress-Induced Corticosterone Secretion in the Rat L inda P atia Lanier, C arol Van H artesveldt1, Bonita J. W eis and R. L. Isaacson1 University of Florida, Gainesville, Fla.
Key Words. Hippocampus • Stress • Diurnal corticosterone Abstract. The effects of dorsal, ventral, and near-total hippocampal lesions upon both rhythmic and stress-induced corticosterone secretion in adult male rats were examined. All hippocampally-damaged, cortically-damaged, and intact rats showed rhythmic corti costerone secretion as measured in 4 blood samples for each animal taken at 6-h intervals at least 1 week apart. There were no significant differences among the groups. In addition, there were no significant differences in the amount of stress-induced corticosterone across experimental groups.
The hippocampus has been implicated in the regulation of the hypo thalamic-hypophyseal-adrenocortical system by the results of experiments involving electrical stimulation of the hippocampus, corticosteroid implants in the hippocampus, and lesions of the hippocampus. However, several recent studies have indicated that near-total ablation of the hippocampus in the rat results in no significant changes in corticosterone either at various points in the diurnal cycle or in response to several stressful stimuli [Coover et al., 1971; W ilson and C ritchlow , 1973/74; K earley et al., 1974], Since manip ulations of small regions of the hippocampus by stimulation, hormone im plants, or electrolytic lesions alter adrenocortical secretion while destruction of most of the structure does not, it is possible that the hippocampus is regionally organized with respect to excitatory and inhibitory regulatory in fluences on the hypothalamic-hypophyseal-adrenocortical system. Inactiva-
Received: February 3rd, 1975; revised MS accepted: April 26th, 1975.
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:20:34 PM
1 This research was supported in part by grant NIH-MH-22199-01 to C.V.H., and grant NIH-M H-16384-04 to R.L.I.
Lanier/V an H artesveldt/W eis,'Isaacson
155
tion of a localized portion of the hippocampus might lead to an imbalance between these regulatory control mechanisms which could be reflected in altered corticosterone production, whereas the inactivation of the entire structure might result in only a temporary functional disturbance of the system. Evidence indicates that the dorsal and ventral hippocampus are dif ferentiated with respect to neuroanatomical innervation and projections [Siegel and T assoni, 1971a, b], behavioral effects of lesions [E llen et al., 1964; H addad and R abe, 1967; L anier and Isaacson, 1975], and responses to implanted corticosteroid hormones [Bohus et al., 1968]. In this study the hypothesis that selective damage to the dorsal or ventral hippocampus might have different effects than large, near-total destruction of the hippocampus on diurnal and/or stress-induced corticosterone secretion was examined.
Subjects. 55 Long-Evans hooded rats of approximately 500 g at the beginning of the blood-sampling procedure were used. Most animals were previously used in a study examining the effects of differential hippocampal lesions on open field activity and response to amphetamine in the open field [Lanier and Isaacson, 1975]. At least 1 month inter vened between the end of the previous testing and the habituation phase of the present study. Blood sampling began 2-3 months postoperatively. Operative procedure. Clean surgical technique was used. All rats were anesthetized with Nembutal and given 55,000 units Bicillin preoperatively. The lesions were made by aspira tion with a 22-gauge blunt-tipped needle following essentially the same surgical procedures as Isaacson et al. [1961]. In the dorsal hippocampal group (DH), medial-dorsal cortex and the antero-dorsal portion of the hippocampus were removed. More lateral and caudal cortical lesions were made in the ventral hippocampal group (VH) so that ventral hippo campus could be exposed and removed. By combining these two methods, near-total hippocampal (H) lesions were made. In the cortical control group (CC), medial-dorsal and caudal-lateral cortex were removed, exposing the hippocampus but not damaging it. The skull was exposed and drilled but the dura was not damaged in the sham control group (SC). Sampling procedure. At the beginning of the habituation phase of the present study the animals were placed in a private colony room maintained on a 12-12 h light-dark cycle with the light portion of the cycle beginning at 08.00 h. All animals were given at least 2 weeks' adaptation to this colony room before any blood samples were taken. A within-subjects design was used. Each animal was sampled at 07.00, 13.00, 19.00, and 01.00 h for the diurnal cycle determination. At least 1 week intervened between successive blood-sampling sessions for any animal. Data from animals that died during the course of the experiment were excluded from data analysis. For at least 12 h prior to a blood-sampling session no one was admitted to the colony room. Animals were not replaced in the colony room until all animals in that sampling period had been removed and sampled. No more than 7 animals were sampled during a
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Materials and Methods
156
Lanier/V an H artesveldt/W eis/I saacson
Fig. 1. Reconstructions of the minimum (dark, stippled area) and maximum (crosshatched area) lesion extent for each of the brain-damaged groups. Row A illustrates the extent of damage for rats with large hippocampal lesions (Group H); row B illustrates the damage to animals with ventral hippocampal lesions (Group VH); row C illustrates the damage to animals with dorsal hippocampal lesions (Group DH); and row D illustrates the damage to the group of animals sustaining only neocortical damage (Group CQ .
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single 30-45 min sampling period. Each animal was individually removed from the colony room in his home cage and quickly placed in an ether jar. Blood samples of 1.5-2.2 cm3 were taken via intracardiac puncture within 2 min. Blood samples were centrifuged; the serum fraction was then aspirated and frozen for later fluorometric assay for corticosterone. The stress-sampling procedure was begun 1 week or more after the last diurnal cycle sample was taken. The stress-sampling period began at 08.00 h and lasted 45-60 min. Each animal was removed from the colony room, etherized and subjected to intracardiac puncture within a 2-min period but no blood sample was drawn. Each animal was then placed in his home cage in the sampling room and re-etherized 15 min later. Blood samples were then taken within 2 min after initiation of this second etherization. Assay procedure. Plasma corticosterone was measured fluorometrically following the basic procedure of Silber el at. [1958], All samples were assayed in triplicate. Assays were repeated in duplicate or triplicate when a lack of consistency was found over the samples or when samples were inadvertently lost during the assay procedure.
Differential Hippocampal Damage and Corticosterone Secretion
157
Histology. Rats were given injections of an overdose of Nembutal and intracardially perfused consecutively with physiological saline and a 10% formalin solution. The brains were removed, embedded in celloidin and cut coronally at 30 ft. Every eighth section was mounted and stained with thionin. The slides were examined and the extent of damage was drawn onto serial brain section diagrams. Rats were discarded from the study if they sustained moderate damage outside the target areas.
Results
Corticosterone Assay Five separate Kruskal-Wallis one-way analyses of variance on the data across the experimental groups at each of the time periods and with the stress sampling revealed no significant differences between groups at any of these sampling periods (see fig. 2, 3). Friedman two-way analyses of variance on the data within each group across the 4 time periods were found to be significant for each of the groups (DH : x2 = 10.62, df = 3, p < 0.02; VH : x2 = 9.96, df = 3, p < 0.02; H : x2 = 13.20, df = 3, p < 0.01; CC : x2 = 13.80, df = 3, p < 0.01; S C : x* = 12.09, df = 3, p< 0.01). A posteriori sign tests determined that the 7 p.m. (19.00 h) values for all groups were significantly greater than the 7 a.m. (07.00 h) and 1 p.m. (13.00 h) values (in these and all subsequent sign tests p < 0 .0 5 was considered to be significant). In addition, in all groups but the SC group the 1 a.m. (01.00 h) values were found to be significantly lower than the 7 p.m. (19.00 h) values. In the CC group the 7 a.m. (07.00 h) values were found to be significantly greater than the 1 p.m. (13.00 h) values. No other of these within-group comparisons was significant. Using sign tests, stress values were compared to the 7 a.m. (07.00 h) control values for each group. These tests revealed that all groups showed a significant increase in corticosterone levels after the stress.
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Histology Data from animals that sustained substantial bilateral damage to the thalamus and/or habenular complex were discarded from the study, as were animals who did not sustain significant bilateral damage to the hippocampal areas in question. The final ‘N’s for each group were: DH-5; VH-5; H-6; CC-8; SC-7. Figure 1 shows the maximum and minimum extent of damage for each of the 4 brain-damaged groups. For a more complete analysis of the damage sustained in each of the hippocampally-damaged groups see Lanier and Isaacson [1975].
158
L anier/V an H artesveldt/W eis/Isaacson
I I
07.00 h 13.00 h
□ 19.00 h 1 01.00 h
Fig. 3. Resting and ether stress levels of plasma corticosterone. Bars indicate group means; vertical lines indicate one standard error of the mean.
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Fig. 2. Resting levels of plasma corticosterone obtained at four 6-h intervals. Bars indicate group means; vertical lines indicate one standard error of the mean.
Differential Hippocampal Damage and Corticosterone Secretion
159
Discussion The hypothesis that the hippocampus might be organized in a dorsalventral dimension with respect to modulation of pituitary-adrenocortical activity was not supported by the results of the present experiment. Neither the rats with selective lesions nor those rats with more complete hippocampal destruction showed any alteration in the circadian rhythm of corticosterone secretion or in stress-induced corticosterone release. The present results are thus consistent with previous work showing that large, near-total hippo campal lesions have no effect on trough levels [Coover et al., 1971; K earley et al., 1974] or diurnal levels of corticosterone [Wilson and C ritchlow , 1973/74]. Furthermore, our results show that the dorsal and ventral hippo campus are not the locus of the hypothesized regional localization of control mechanisms of corticosterone secretion within the hippocampus. Thus, the lack of effects with large hippocampal lesions does not appear to be due to a masking produced by destruction of opposing modulatory centers in dorsal or ventral hippocampus. Similarly, J ackson and R egestein [1974] have shown that neither anterior, nor posterior, nor near-total ablation of the hippo campus in rhesus monkey affects diurnal cortisol secretion. The failure of either large or small hippocampal lesions to affect corti costerone secretion under either resting or stressful conditions must lead to a reconsideration of the generally accepted interpretation that the hippocampus inhibits pituitary-adrenocortical secretion. This interpretation was based primarily on studies showing that electrical stimulation of the hippocampus suppressed stress-induced increases in corticosteroids [e.g., M ason, 1958; Endr Qczi et al., 1959; K awakami et al., 1968], The discrepancies in the interpretations of electrical stimulation and ablation experiments emphasize the problems in generalizing from the results of experiments employing any particular technique, since each technique has its limitations. At present, it is not possible to construct a theory of the role of the hippocampus in the control of this hormone system which is consistent with the results of experiments using different experimental techniques. References Bohus , B.; N yakas, Cs ., and L issak, K.: Involvement of suprahypothalamic structures in
the hormonal feedback action of corticosteroids. Acta physiol, hung. 34: 1-8 (1968). tion of a lever-press response in hippocampectomized animals. Physiol. Behav. 7; 727732 (1971).
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:20:34 PM
Coover, G. D .; G oldman, L., and L evine, S.: Plasma corticosterone levels during extinc
L anier/V an H artesveldt/W eis/Isaacson
160
E llen, P.; W ilson, A.S., and Powell , E .W .: Septal inhibition and timing behavior in
the rat. Expl. Neurol. 10: 120-132 (1964). E ndroczi, E.; L issak, K .; Bohus, B., and K ovacs, S .: The inhibitory influence of archi-
cortical structures on pituitary-adrenal function. Acta physiol, hung. 16: 17-22 (1959). H addad, R. K. and R abe, A .: Effect of selective hippocampal lesions in the rat on DRL-20
acquisition. J. Psychol. Studies 15: 106-124 (1967). Isaacson, R.L.; D ouglas, R.J., and M oore, R.Y.: The effect of radical hippocampal
ablation on acquisition of an avoidance response. J.cornp. physiol. Psychol. 54: 625628 (1961). J ackson, W .J. and R egestein, Q .R .: Hippocampectomy in rhesus monkeys: effects on plasma cortisol during two stressful conditions. 4th Annu. Soc. Neurosci. Meeting, St.Louis, Missouri (1974). K awakami, M .; S eto, K .; T erasawa, E .; Yoshida, K .; M iyamoto, T .; Sekiguchi, M., and H attori, Y .: Influence of electrical stimulation and lesion in limbic structure upon
biosynthesis of adrenocorticoid in the rabbit. Neuroendocrinology 3: 337-348 (1968). K earley, R.C.; Van H artesveldt, C., and W oodruff, M .L.: Behavioral and hormonal
effects of hippocampal lesions on male and female rats. Physiol. Psychol. 2: 187-196 (1974). L anier, L.P. and Isaacson, R.L.: Activity changes related to the location of lesions in the hippocampus. Behav. Biol. 13: 59-69 (1975). M ason, J.W .: The central nervous system regulation of ACTH secretion; in J asper, P roctor, K nighton , N oshay and Costello Reticular formation of the brain, pp. 645662 (Little Brown, Boston 1958). Siegel, A. and T assoni, J. P .: Differential efferent projections from the ventral and dorsal hippocampus of the cat. Brain Behav. Evol. 4: 185-200 (1971a). Siegel, A. and T assoni, J.P .: Differential efferent projections of the lateral and medial septal nucleus to the hippocampus in the cat. Brain Behav. Evol. 4: 201-219 (1971b). Silber, R .H .; Busch, R.D., and O slapas, R.: Practical procedure for elimination of corticosterone or hydrocortisone. Clin. Chem. 4: 278-285 (1958). W ilson, M. and C ritchi.ow , V.: Effect of fornix transection or hippocampectomy on rhythmic pituitary-adrenal function in the rat. Neuroendocrinology 13:29-40 (1973/74).
Downloaded by: King's College London 137.73.144.138 - 1/16/2019 10:20:34 PM
Linda L anier, Box 97, Psychology Department, University of Florida, Gainesville, FL
32611 (USA)
