BEHAVIOm~L mOLOGY 24, 527-532 (1978)
BRIEF REPORT Adrenalectomy Attenuates Electroconvulsive Shock-Induced Retrograde Amnesia in Rats HOWARD
B. BOOKIN AND W.
D E A N P F E I F E R t'g
Department o[" Psychology, Connecticut College, New London, Com~ecticut 06320 and Ribicqflf Research Center, Norwich Hospital, Norwich, Com, ecticut 06360 The i n v o l v e m e n t of the adrenal glands in the induction of electroconvulsiveshock a m n e s i a was examined. Sham-adrenalectomized rats given an electroconvulsive s h o c k immediately following a single passive avoidance acquisition trial showed a m n e s i a w h e n tested 24 hr after training. Bilateral a d r e n a l e c t o m y 10 days before training protected rats against the disruptive effects of electroconvulsive s h o c k on p a s s i v e avoidance behavior.
The role of the pituitary-adrenal system in learning and/or memory processes has been well documented (DeWied, 1974). The administration of pituitary peptide hormones such as adrenocorticotrophic hormone (ACTH) o1" lysine vasopressin (LVP) strengthens both active and passive avoidance responding in intact or hypophysectomized rats (Bohus et al., 1972; Bohus et al., 1973; DeWied, 1966, 1971; Levine and Jones, 1965). Adrenal glucocorticoids have the opposite effect, weakening avoidance responding (Bohus et al., 1970; Bohus and Lissfi.k, 1968; DeWied, 1967; Kovfics et al., 1977; Van Wimersma Greidanus, 1977). Consistent with these findings are the results that adrenalectomy, which produces a sustained elevation of plasma ACTH (Matsuyama et al., 1971; Mims, 1973) enhances passive and active avoidance responding (Weiss et al., 1970). These behavioral alterations appear to be due to the lack of adrenal corticosteroids following adrenalectomy and not deficiencies of catecholamines of the adrenal medulla (Silva, 1973). Adrenalectomy has also been shown to prevent the amnesic effects of the protein synthesis inhibitors puromycin (Flexner and Flexner, 1970) and cycloheximide (Nakajima, 1975). Kindled convulsions of the amyg1 We gratefully acknowledge A n n e Conkin for her assistance and Mrs. Dolores Desrosiers for help preparing the manuscript. -' To w h o m reprint requests should be addressed.
527 0091-6773/78/0244-0527502.00/0 Copyright @ 1978by Academic Press. Inc. All rights of reproduction in any form reserved.
528
BOOKIN AND PFEIFER
dala induce retrograde amnesia, which is also blocked by adrenalectomy (McIntyre, 1976). We now report effects of adrenalectomy on electroconvulsive shock (ECS)-induced amnesia. Forty male Sprague-Dawley-derived rats, weighing 290 to 390 g were attained from the Charles River Breeding Laboratories. A 12-hr light/12hr dark cycle from 6:00 AM to 6:00 PM was in effect and room temperature was maintained to 21 to 23°C. Animals were housed in pairs in wire mesh cages (37 × 18 x 23 cm) with food and water available ad libitum. All animals were anesthetized with Nembutal (50 mg/kg) and received 0.3 ml of atropine sulfate (0.5 mg/ml). The adrenal glands were exposed bilaterally via the dorsal approach and either excised (ADX) or left intact (sham ADX). Adrenalectomized animals were maintained on 0.9% NaC1 throughout the experiment. Ten days after the surgical procedure all animals were trained in passive avoidance as described by Booklin and Pfeifer (1977). Each rat was given a single passive avoidance training trial. One minute after the animal was placed in the start box, the door to the darkened chamber was opened, automatically starting a timer that measured step-through latency time. One second after the rear legs of the rat passed into the darkened chamber, the grid floor was electrified by a scrambled shock generator set to deliver a shock intensity of 0.4 mA for 3 sec. All animals were removed from the shock chamber 7 sec after the termination of the shock. Immediately on termination of the acquisition trial, groups 1 (ADXECS) and 3 (sham ADX-EDS; were given the amnesic treatment. ECS was administered through ear clips with a current of 100 mA for 0.3 sec. Groups 2 (ADX-sham ECS) and 4 (sham ADX-sham ECS) received sham amnesic treatment; ear clips were attached, but no current was delivered. Twenty-four and forty-eight hours after the acquisition trial, each animal was again placed in the start box for 1 rain. Step-through latencies to enter the shock chamber were measured to a maximum of 300 sec. Animals entering the shock chamber during the test trials were removed after 10 sec. During the 24-hr test, any animal that reached the maximum latency was placed in the shock chamber for 10 sec. Shock was not presented during either test. One day after the conclusion of the experiment, the completeness of adrenalectomy was verified. Each animal was sacrificed by decapitation 15 rain after ECS administration and serum corticosterone was assayed fluorometrically by the method of Silber et al. (1958). Visual inspection was also performed. None of the animals assigned to the ADX groups had elevated corticosterone levels in response to ECS, while there was a three-fold elevation of the hormone in control animals. The median step-through latencies for the training trial were less than 19 sec for all groups. No differences were observed between the ADX and
A D R E N A L E C T O M Y AND ECS A M N E S I A
529
sham ADX groups during the acquisition trial. Median step-through latencies for the test trials are presented in Table !. A Friedman two-way analysis of variance indicated that passive avoidance conditioning occurred in the sham ADX-sham ECS group with a significant increase in response latency 24 hr after presentation of shock (X2 = 9.99, P < 0.002). Group by group comparisons were made by means of Mann-Whitney U tests. Convulsions were exhibited in both groups receiving ECS. Adrenalectomy did not result in any observable effects on the convulsion. Compared to the sham ADX-sham ECS group, the sham ADX-ECS group showed amnesia at both the 24 (U - 8, P < 0.002), and 48 hr (U = 11, P < 0.02) retention tests. Adrenalectomy (ADX-sham ECS) did not facilitate avoidance responding when compared to the sham control group (sham ADX-sham ECS). Those animals adrenalectomized and receiving ECS (ADX-ECS) were resistant to the amnesic effect of ECS at both the 24 (U = 5, P < 0.002) and 48 hr (U = 0, P < 0.002) retention tests (compared to the sham ADX-ECS group). The results of the present study clearly show that the removal of adrenal hormones antagonizes the retrograde amnesia induced by electroconvulsive shock. Adrenalectomy antogonizes the amnesia induced by both protein synthesis inhibitors and convulsant agents. Adrenal hormones may play a permissive role in the induction of amnesia. We would not want to imply, however, that these different treatments which all TABLE 1
Median Step-Through Latencies during Test Trials for All Groups Median retest latency (interquartile range) (sec) Group
Treatment
N
24 H o u r
48 Hour
1
ADX-ECS a
10
2
A D X - s h a m ECS
10
3
Sham A D X - E C S
9
300 ~ (300-300) 237 (78-300 37 c
300 b (300-300) 300 (115-300) 20 a
10
(14-65) 147
(12-26) 130
(101-287)
(42-263)
4
Sham A D X - s h a m ECS
a ADX, Adrenalectomy; sham ADX, sham adrenalectomy (adrenals intact); ECS, electroconvulsive shock; sham ECS, sham amnesic treatment. b Significantly different from sham ADX-ECS group, P < 0.002 (two-tailed MannWhitney U test). c Significantly different from sham A D X - s h a m ECS group, P < 0.002 (two-tailed Mann-Whitney U test). a Significantly different from sham A D X - s h a m ECS group, P < 0.02 (two-tailed MannWhitney U test).
530
BOOKIN AND PFEIFER
disrupt memory processes, bring about the alteration in the behavioral end point of passive avoidance responding by the same mechanism. In fact, it appears that the mechanisms may indeed be different. Nakajima (1975) has suggested that protein synthesis inhibitors induce amnesia due to the suppression of adrenocortical steroidogenesis and not by inhibiting cerebral protein synthesis. This hypothesis would seem untenable in view of the findings that drugs which inhibit steroidogenesis but do not affect protein synthesis are unable to induce amnesia (Squire et al., 1976; Dunn and Leibmann, 1977). Also, in the present study as well as others (Nakajima, 1975), adrenalectomy, which suppresses steroidogenesis, does not result in amnesia. In order to deal with this problem, Nakajima (1975) proposed state-dependent learning in that steroid suppression by cycloheximide during training coupled with normal production at testing produced the amnesia. It was later shown that cycloheximide did not produce state-dependent learning (Nakamima, 1975, as cited by Cottrell and Nakajima, 1977). The lack of support for these protein synthesis inhibitors acting via a periphe(al adrenal mechanism does not, however, confirm the hypothesized central mechanism. It is clear that central nervous system protein synthesis can be appreciably inhibited without blocking memory (Flexner and Flexner, 1970; Nakajima, 1975). It would seem that it must be concluded that the mechanism of memory disruption by protein synthesis inhibitors is unknown. Convulsant agents may bring about amnesia by a peripheral mechanism. One plausible mechanism would involve the elevation of adrenocorticoids in response to the convulsant agent. One must again assume state-dependent learning, but in this case there would be high levels of corticosteroids at the time of training due to the convulsant agents and low levels at the time of testing. Consistent with this suggestion is the report by McIntyre (1976) that adrenalectomy antagonizes amensia induced by kindled convulsions of the amygdala. Adrenalectomized animals did not differ from intact animals with respect to the overt seizure or the electrical activity in the central nervous system indicating a peripheral rather than central mechanism underlying the amnesia. Also, several papers have reported a disruption of passive avoidance behavior by high levels of corticosterone (Bohus et al., 1970; Kovfics et a/., 1977; Van Wimersma Greidanus, 1977). It is also possible that the adrenal glands are not involved in the induction of amnesia by convulsant agents at all and the results of the present study are due to other effects occurring as a result of the adrenalectomy. Adrenalectomy is known to produce sustained elevations of ACTH (Matsuyama et al., 1971; Mims, 1973), and this peptide hormone and some analogs of it have been shown to overcome the amnesia produced by ECS (Keyes, 1974) and CO., (Rigter et al., 1974). Adrenalectomy also blocks the amnesia induced by cycloheximide (Nakajima, 1975) and
531
ADRENALECTOMY AND ECS AMNESIA
puromycin (Flexner and Flexner, 1970). It s e e m s p o s s i b l e t h a t t h e adrenalectomy-induced a t t e n u a t i o n o f a m n e s i a in g e n e r a l is m e d i a t e d b y the increased
level of ACTH
following adrenalectomy,
or perhaps
some
o t h e r n e u r o p e p t i d e ( G u i l l e m i n e t a l . , 1977). C u r r e n t r e s e a r c h is d i r e c t e d a t assessing this possibility.
REFERENCES Bohus, B., Ader, R., and DeWied, D. (1972). Effects of vasopressin on active and passive avoidance behavior. Horm. Behav. 3, 191-197. Bohus, B., Gispen, W. H., and DeWied, D. (1973). Effect oflysine vasopressin and ACTH 4-10 on conditioned avoidance behavior of hypophysectomized rats. Nearoendocrinology 11, 137-143. Bohus, B., GruNts, J., Kovfics, G., and Lissfik, K. (1970). Effect of corticosteroids on passive avoidance behavior of rats. Acta Physiol. Acad. Sci. Htmg. 38, 381-391. Bohus, B., and Lissfik, K. (1968). Adrenocortical hormones and avoidance behaviour of rats. Int. J. Neuropharmacol. 7, 301-306. Bookin, H. B., and Pfeifer, W. D. (1977). Effect oflysine vasopressin on pentylenetetrazolinduced retrograde amnesia in rats. Pharmacol. Biochem. Behav. 7, 51-54. Cottrell, G. A., and Nakajima, S. (1977). Effect of corticosteroids in the hippocampus on passive avoidance behavior in the rat. Pharmacol. Biochem. Behav. 7, 277-280. DeWied, D. (1966). Inhibitory effect of ACTH and related peptides on extinction of conditioned avoidance behavior in rats. Proc. Soc. Exp. Biol. Med. 122, 28-32. DeWied, D. (1967). Opposite effects of ACTH and glucocorticosteroids on extinction of conditioned avoidance behavior. Excerpta Medica, Int. Congr. Series No. 132. 132, 945-951. DeWied, D. (1971). Long-term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. (London) Nature 232, 58-60. DeWied, D. (1974). Pituitary-adrenal system hormones and behavior. In F. O. Schmidt and F. G. Worden (Eds.), "The Neurosciences Third Study Program," pp. 653-666. Cambridge: MIT Press. Dunn, A. J., and Leibmann, S. (1977). The amnestic effect of protein synthesis inhibitors is not due to the inhibition of adrenal corticosteroidogenesis. Behav. Biol. 19, 411-416. Flexner, J. B., and Flexner. L. B. (1970). Adrenalectomy and the suppression of memory by puromycin. Proc. Natl. Acad. Sci. 66, 48-52. Guillemin, R., Vargo, T., Rossier, J., Minick, S., Ling, N., Rivier, C., Vale, W., and Bloom, F. (1977). /~-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197, 1367-1369. Keyes, J. B. (1974). Effect of ACTH on ECS-produced amnesia of a passive avoidance task. Physiol. Psychol. 2, 307-309. Kovfics, G. L., Telegdy, G., and Liss~.k, K. (1977). Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior. Horm. Behav. 8, 155-165. Levine, S., and Jones, L. E. (1965). Adrenocorticotrophic hormone (ACTH) and passive avoidance learning. J. Comp. Physiol. Psychol. 59, 357-360. Matsuyama, H., Mims, R. B., Ruhmann-Wennhold, A., and Nelson, D. H. (1971). Bioassay and radioimmunoassay of plasma ACTH in adrenalectomized rats. Endocrinology 88, 696-701. Mclntyre, D. C. (1976). Adrenalectomy: Protection from kindled convulsion induced amnesia in rats. Physiol. Behav. 17, 789-795. Mims, R. B. (1973). Plasma ACTH in the adrenalectomized rat. Horm. Metab. Res. 5, 368-371. Nakajima, S. (1975). Amnesic effect of cycloheximide in the mouse mediated by adrenocortical hormones. J. Comp. Physiol. Psychol. 88, 378-385.
532
BOOKIN AND PFEIFER
Rigter, H., van Riezen, H., and DeWied, D. (1974). The effects of ACTH and vasopressinanalogues on CO2-induced retrograde amnesia in rats. Physiol. Behav. 13, 381-388. Silber, R. H., Busch, R. D., and Oslapas, R. (1958). Practical procedure for estimation of corticosterone or hydrocortisone. Clin. Chem. 4, 278-285. Silva, M. T. A. (1973). Extinction of a passive avoidance response in adrenalectomized and demedullated rats. Behav. Biol. 9, 553-562. Squire, L. R., St. John, C., and Davis, H. P. (1976). Inhibition of protein synthesis and memory dissociation of amnesic effects and effects on adrenal steroidogenesis. Brain Res. 112, 200-206. Van Wimersma Greidanus, Tj. B. (1977). Pregnene-type steroids and impairment of passive avoidance behavior in rats. Horm. Behav. 9, 49-56. Weiss, J. M., McEwen, B. S., Silva, M. T. and Kalbut, M. (1970). Pituitary-adrenal alterations and fear responding. Ames'. J. Physiol. 218, 864-868.
BRIEF REPORT Adrenalectomy Attenuates Electroconvulsive Shock-Induced Retrograde Amnesia in Rats HOWARD
B. BOOKIN AND W.
D E A N P F E I F E R t'g
Department o[" Psychology, Connecticut College, New London, Com~ecticut 06320 and Ribicqflf Research Center, Norwich Hospital, Norwich, Com, ecticut 06360 The i n v o l v e m e n t of the adrenal glands in the induction of electroconvulsiveshock a m n e s i a was examined. Sham-adrenalectomized rats given an electroconvulsive s h o c k immediately following a single passive avoidance acquisition trial showed a m n e s i a w h e n tested 24 hr after training. Bilateral a d r e n a l e c t o m y 10 days before training protected rats against the disruptive effects of electroconvulsive s h o c k on p a s s i v e avoidance behavior.
The role of the pituitary-adrenal system in learning and/or memory processes has been well documented (DeWied, 1974). The administration of pituitary peptide hormones such as adrenocorticotrophic hormone (ACTH) o1" lysine vasopressin (LVP) strengthens both active and passive avoidance responding in intact or hypophysectomized rats (Bohus et al., 1972; Bohus et al., 1973; DeWied, 1966, 1971; Levine and Jones, 1965). Adrenal glucocorticoids have the opposite effect, weakening avoidance responding (Bohus et al., 1970; Bohus and Lissfi.k, 1968; DeWied, 1967; Kovfics et al., 1977; Van Wimersma Greidanus, 1977). Consistent with these findings are the results that adrenalectomy, which produces a sustained elevation of plasma ACTH (Matsuyama et al., 1971; Mims, 1973) enhances passive and active avoidance responding (Weiss et al., 1970). These behavioral alterations appear to be due to the lack of adrenal corticosteroids following adrenalectomy and not deficiencies of catecholamines of the adrenal medulla (Silva, 1973). Adrenalectomy has also been shown to prevent the amnesic effects of the protein synthesis inhibitors puromycin (Flexner and Flexner, 1970) and cycloheximide (Nakajima, 1975). Kindled convulsions of the amyg1 We gratefully acknowledge A n n e Conkin for her assistance and Mrs. Dolores Desrosiers for help preparing the manuscript. -' To w h o m reprint requests should be addressed.
527 0091-6773/78/0244-0527502.00/0 Copyright @ 1978by Academic Press. Inc. All rights of reproduction in any form reserved.
528
BOOKIN AND PFEIFER
dala induce retrograde amnesia, which is also blocked by adrenalectomy (McIntyre, 1976). We now report effects of adrenalectomy on electroconvulsive shock (ECS)-induced amnesia. Forty male Sprague-Dawley-derived rats, weighing 290 to 390 g were attained from the Charles River Breeding Laboratories. A 12-hr light/12hr dark cycle from 6:00 AM to 6:00 PM was in effect and room temperature was maintained to 21 to 23°C. Animals were housed in pairs in wire mesh cages (37 × 18 x 23 cm) with food and water available ad libitum. All animals were anesthetized with Nembutal (50 mg/kg) and received 0.3 ml of atropine sulfate (0.5 mg/ml). The adrenal glands were exposed bilaterally via the dorsal approach and either excised (ADX) or left intact (sham ADX). Adrenalectomized animals were maintained on 0.9% NaC1 throughout the experiment. Ten days after the surgical procedure all animals were trained in passive avoidance as described by Booklin and Pfeifer (1977). Each rat was given a single passive avoidance training trial. One minute after the animal was placed in the start box, the door to the darkened chamber was opened, automatically starting a timer that measured step-through latency time. One second after the rear legs of the rat passed into the darkened chamber, the grid floor was electrified by a scrambled shock generator set to deliver a shock intensity of 0.4 mA for 3 sec. All animals were removed from the shock chamber 7 sec after the termination of the shock. Immediately on termination of the acquisition trial, groups 1 (ADXECS) and 3 (sham ADX-EDS; were given the amnesic treatment. ECS was administered through ear clips with a current of 100 mA for 0.3 sec. Groups 2 (ADX-sham ECS) and 4 (sham ADX-sham ECS) received sham amnesic treatment; ear clips were attached, but no current was delivered. Twenty-four and forty-eight hours after the acquisition trial, each animal was again placed in the start box for 1 rain. Step-through latencies to enter the shock chamber were measured to a maximum of 300 sec. Animals entering the shock chamber during the test trials were removed after 10 sec. During the 24-hr test, any animal that reached the maximum latency was placed in the shock chamber for 10 sec. Shock was not presented during either test. One day after the conclusion of the experiment, the completeness of adrenalectomy was verified. Each animal was sacrificed by decapitation 15 rain after ECS administration and serum corticosterone was assayed fluorometrically by the method of Silber et al. (1958). Visual inspection was also performed. None of the animals assigned to the ADX groups had elevated corticosterone levels in response to ECS, while there was a three-fold elevation of the hormone in control animals. The median step-through latencies for the training trial were less than 19 sec for all groups. No differences were observed between the ADX and
A D R E N A L E C T O M Y AND ECS A M N E S I A
529
sham ADX groups during the acquisition trial. Median step-through latencies for the test trials are presented in Table !. A Friedman two-way analysis of variance indicated that passive avoidance conditioning occurred in the sham ADX-sham ECS group with a significant increase in response latency 24 hr after presentation of shock (X2 = 9.99, P < 0.002). Group by group comparisons were made by means of Mann-Whitney U tests. Convulsions were exhibited in both groups receiving ECS. Adrenalectomy did not result in any observable effects on the convulsion. Compared to the sham ADX-sham ECS group, the sham ADX-ECS group showed amnesia at both the 24 (U - 8, P < 0.002), and 48 hr (U = 11, P < 0.02) retention tests. Adrenalectomy (ADX-sham ECS) did not facilitate avoidance responding when compared to the sham control group (sham ADX-sham ECS). Those animals adrenalectomized and receiving ECS (ADX-ECS) were resistant to the amnesic effect of ECS at both the 24 (U = 5, P < 0.002) and 48 hr (U = 0, P < 0.002) retention tests (compared to the sham ADX-ECS group). The results of the present study clearly show that the removal of adrenal hormones antagonizes the retrograde amnesia induced by electroconvulsive shock. Adrenalectomy antogonizes the amnesia induced by both protein synthesis inhibitors and convulsant agents. Adrenal hormones may play a permissive role in the induction of amnesia. We would not want to imply, however, that these different treatments which all TABLE 1
Median Step-Through Latencies during Test Trials for All Groups Median retest latency (interquartile range) (sec) Group
Treatment
N
24 H o u r
48 Hour
1
ADX-ECS a
10
2
A D X - s h a m ECS
10
3
Sham A D X - E C S
9
300 ~ (300-300) 237 (78-300 37 c
300 b (300-300) 300 (115-300) 20 a
10
(14-65) 147
(12-26) 130
(101-287)
(42-263)
4
Sham A D X - s h a m ECS
a ADX, Adrenalectomy; sham ADX, sham adrenalectomy (adrenals intact); ECS, electroconvulsive shock; sham ECS, sham amnesic treatment. b Significantly different from sham ADX-ECS group, P < 0.002 (two-tailed MannWhitney U test). c Significantly different from sham A D X - s h a m ECS group, P < 0.002 (two-tailed Mann-Whitney U test). a Significantly different from sham A D X - s h a m ECS group, P < 0.02 (two-tailed MannWhitney U test).
530
BOOKIN AND PFEIFER
disrupt memory processes, bring about the alteration in the behavioral end point of passive avoidance responding by the same mechanism. In fact, it appears that the mechanisms may indeed be different. Nakajima (1975) has suggested that protein synthesis inhibitors induce amnesia due to the suppression of adrenocortical steroidogenesis and not by inhibiting cerebral protein synthesis. This hypothesis would seem untenable in view of the findings that drugs which inhibit steroidogenesis but do not affect protein synthesis are unable to induce amnesia (Squire et al., 1976; Dunn and Leibmann, 1977). Also, in the present study as well as others (Nakajima, 1975), adrenalectomy, which suppresses steroidogenesis, does not result in amnesia. In order to deal with this problem, Nakajima (1975) proposed state-dependent learning in that steroid suppression by cycloheximide during training coupled with normal production at testing produced the amnesia. It was later shown that cycloheximide did not produce state-dependent learning (Nakamima, 1975, as cited by Cottrell and Nakajima, 1977). The lack of support for these protein synthesis inhibitors acting via a periphe(al adrenal mechanism does not, however, confirm the hypothesized central mechanism. It is clear that central nervous system protein synthesis can be appreciably inhibited without blocking memory (Flexner and Flexner, 1970; Nakajima, 1975). It would seem that it must be concluded that the mechanism of memory disruption by protein synthesis inhibitors is unknown. Convulsant agents may bring about amnesia by a peripheral mechanism. One plausible mechanism would involve the elevation of adrenocorticoids in response to the convulsant agent. One must again assume state-dependent learning, but in this case there would be high levels of corticosteroids at the time of training due to the convulsant agents and low levels at the time of testing. Consistent with this suggestion is the report by McIntyre (1976) that adrenalectomy antagonizes amensia induced by kindled convulsions of the amygdala. Adrenalectomized animals did not differ from intact animals with respect to the overt seizure or the electrical activity in the central nervous system indicating a peripheral rather than central mechanism underlying the amnesia. Also, several papers have reported a disruption of passive avoidance behavior by high levels of corticosterone (Bohus et al., 1970; Kovfics et a/., 1977; Van Wimersma Greidanus, 1977). It is also possible that the adrenal glands are not involved in the induction of amnesia by convulsant agents at all and the results of the present study are due to other effects occurring as a result of the adrenalectomy. Adrenalectomy is known to produce sustained elevations of ACTH (Matsuyama et al., 1971; Mims, 1973), and this peptide hormone and some analogs of it have been shown to overcome the amnesia produced by ECS (Keyes, 1974) and CO., (Rigter et al., 1974). Adrenalectomy also blocks the amnesia induced by cycloheximide (Nakajima, 1975) and
531
ADRENALECTOMY AND ECS AMNESIA
puromycin (Flexner and Flexner, 1970). It s e e m s p o s s i b l e t h a t t h e adrenalectomy-induced a t t e n u a t i o n o f a m n e s i a in g e n e r a l is m e d i a t e d b y the increased
level of ACTH
following adrenalectomy,
or perhaps
some
o t h e r n e u r o p e p t i d e ( G u i l l e m i n e t a l . , 1977). C u r r e n t r e s e a r c h is d i r e c t e d a t assessing this possibility.
REFERENCES Bohus, B., Ader, R., and DeWied, D. (1972). Effects of vasopressin on active and passive avoidance behavior. Horm. Behav. 3, 191-197. Bohus, B., Gispen, W. H., and DeWied, D. (1973). Effect oflysine vasopressin and ACTH 4-10 on conditioned avoidance behavior of hypophysectomized rats. Nearoendocrinology 11, 137-143. Bohus, B., GruNts, J., Kovfics, G., and Lissfik, K. (1970). Effect of corticosteroids on passive avoidance behavior of rats. Acta Physiol. Acad. Sci. Htmg. 38, 381-391. Bohus, B., and Lissfik, K. (1968). Adrenocortical hormones and avoidance behaviour of rats. Int. J. Neuropharmacol. 7, 301-306. Bookin, H. B., and Pfeifer, W. D. (1977). Effect oflysine vasopressin on pentylenetetrazolinduced retrograde amnesia in rats. Pharmacol. Biochem. Behav. 7, 51-54. Cottrell, G. A., and Nakajima, S. (1977). Effect of corticosteroids in the hippocampus on passive avoidance behavior in the rat. Pharmacol. Biochem. Behav. 7, 277-280. DeWied, D. (1966). Inhibitory effect of ACTH and related peptides on extinction of conditioned avoidance behavior in rats. Proc. Soc. Exp. Biol. Med. 122, 28-32. DeWied, D. (1967). Opposite effects of ACTH and glucocorticosteroids on extinction of conditioned avoidance behavior. Excerpta Medica, Int. Congr. Series No. 132. 132, 945-951. DeWied, D. (1971). Long-term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. (London) Nature 232, 58-60. DeWied, D. (1974). Pituitary-adrenal system hormones and behavior. In F. O. Schmidt and F. G. Worden (Eds.), "The Neurosciences Third Study Program," pp. 653-666. Cambridge: MIT Press. Dunn, A. J., and Leibmann, S. (1977). The amnestic effect of protein synthesis inhibitors is not due to the inhibition of adrenal corticosteroidogenesis. Behav. Biol. 19, 411-416. Flexner, J. B., and Flexner. L. B. (1970). Adrenalectomy and the suppression of memory by puromycin. Proc. Natl. Acad. Sci. 66, 48-52. Guillemin, R., Vargo, T., Rossier, J., Minick, S., Ling, N., Rivier, C., Vale, W., and Bloom, F. (1977). /~-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197, 1367-1369. Keyes, J. B. (1974). Effect of ACTH on ECS-produced amnesia of a passive avoidance task. Physiol. Psychol. 2, 307-309. Kovfics, G. L., Telegdy, G., and Liss~.k, K. (1977). Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior. Horm. Behav. 8, 155-165. Levine, S., and Jones, L. E. (1965). Adrenocorticotrophic hormone (ACTH) and passive avoidance learning. J. Comp. Physiol. Psychol. 59, 357-360. Matsuyama, H., Mims, R. B., Ruhmann-Wennhold, A., and Nelson, D. H. (1971). Bioassay and radioimmunoassay of plasma ACTH in adrenalectomized rats. Endocrinology 88, 696-701. Mclntyre, D. C. (1976). Adrenalectomy: Protection from kindled convulsion induced amnesia in rats. Physiol. Behav. 17, 789-795. Mims, R. B. (1973). Plasma ACTH in the adrenalectomized rat. Horm. Metab. Res. 5, 368-371. Nakajima, S. (1975). Amnesic effect of cycloheximide in the mouse mediated by adrenocortical hormones. J. Comp. Physiol. Psychol. 88, 378-385.
532
BOOKIN AND PFEIFER
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