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Post-trial hormonal treatment effects: memory modulation or perceptual distortion?
Journal of Neuroscience Methods, 22 (1987) 27-30
27
Elsevier NSM 00706
Post-trial hormonal treatment effects: memory modulation or perceptual distortion? R o b e r t J. C a r e y s. U.N. E Health Science Center and V.A. Medical Center, Syracuse, N Y (U.S.A.)
(Received 2 September 1986) (Revised 28 January 1987) (Accepted 30 January 1987)
K e y words: M e m o r y ; H o r m o n e ; Passive a v o i d a n c e ; E p i n e p h r i n e
An extensive literature has developed in recent years demonstrating that a variety of peripheral-acting hormonal and pharmacological treatments, administered in post-trial learning paradigms, can substantially influence memory. Careful analysis of the effects of such treatments in passive avoidance paradigms has provided evidence for an interaction between these treatments and the hormonal and physiological events triggered by the noxious stimulation used to induce passive avoidance behavior. The argument developed in this paper is that such post-trial manipulations distort the relationship between the intensity of the noxious stimulus and its physiological sequelae. Considered in this light, changes in passive avoidance behavior appear to represent perceptual distortions rather than memory effects, per se. That is, rather than interfering or enhancing memory processes, peripheral hormonal treatments may simply produce distortions in the perceived intensity of the noxious stimulus.
A n i m a l learning p a r a d i g m s have been used extensively to investigate biological variables which m a y c o n t r i b u t e to the m e d i a t i o n a n d m o d u l a t i o n of m e m o r y processes. Typically, simple l e a r n i n g s i t u a t i o n s have b e e n e m p l o y e d which involve beh a v i o r a l m o d i f i c a t i o n b y r e w a r d or p u n i s h m e n t contingencies. In these studies biological treatm e n t s have p r o d u c e d a l t e r a t i o n s in b e h a v i o r indicative of interference or i m p r o v e m e n t in m e m o r y function. W h i l e no exogenous p h a r m a c o l o g i c a l o r h o r m o n a l m a n i p u l a t i o n c o u l d be expected to exactly d u p f i c a t e the m y r i a d of s e n s o r y - m o t o r events which constitute the m e m o r y trace o f even the simplest l e a r n e d behavior, a p p l i c a t i o n of biological m a n i p u l a t i o n s to m o d i f y m n e m o n i c processes h a v e b e e n g u i d e d b y the a s s u m p t i o n that storage a n d retrieval processes can be m o d u l a t e d b y o r g a n i s m i c state variables. T h e p r o b l e m has been, however, to t r a n s l a t e effects on b e h a v i o r a l perforCorrespondence: R.J. Carey, Res. and Dev. Serv., V.A. Medical Center, 800 Irving Ave., Syracuse, NY 13210, U.S.A.
m a n c e into direct influences on m e m o r y m e c h a nisms. W h e n the e x p e r i m e n t a l m a n i p u l a t i o n s are p e r f o r m e d either p r i o r to or d u r i n g a l e a r n i n g s i t u a t i o n a n y n u m b e r of o r g a n i s m i c effects of the t r e a t m e n t which are o n l y i n d i r e c t l y related to m e m o r y m a y influence test p e r f o r m a n c e (e.g., alterations in s e n s o r y - m o t o r function, changes in m o t i v a t i o n o r arousal, a n d even m o d i f i c a t i o n s in the efficacy of r e w a r d s a n d p u n i s h m e n t s ) . W h i l e these indirect effects are i n h e r e n t l y interesting in the s t u d y o f the biological s u b s t r a t e s for b e h a v i o r they can c o n f o u n d assessment of direct influences o f the biological t r e a t m e n t s on associative m e c h a nisms. P r o b l e m s involved with i n t e r p r e t i n g perform a n c e effects in terms of p s y c h o l o g i c a l processes are n o t unique to the s t u d y of m e m o r y b u t are a long s t a n d i n g f o r m i d a b l e issue in b r a i n - b e h a v i o r research ( L i e b m a n , 1983). A n a l t e r n a t i v e to a d m i n i s t e r i n g biological treatm e n t s p r i o r to or d u r i n g a l e a r n i n g task is to treat the a n i m a l after the task is p e r f o r m e d . T h e distinct a d v a n t a g e of a p o s t - t r i a l p a r a d i g m is that the
0165-0270/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)
28 effects of a treatment variable can be assessed during subsequent tests when the physiological influences of the treatment have subsided. Using this design, a number of physio-chemical manipulations of brain function have been shown to impair or facilitate subsequent task performance. Interpretations of these findings have often been guided by the facile assumption that post-trial treatment effects are direct effects upon memory mechanisms. In early studies, post-trial effects were observed following experimenter-induced alterations of central nervous system function. More recently, however, a number of reports have shown that post-trial administration of peripherally acting hormonal or pharmacological treatments can substantially influence subsequent test performance (McGaugh, 1983; McGaugh et al., 1986). Certainly, one must consider the possibility of a dynamic interplay between the peripheral and central nervous system. Indeed, the first systematic attempt to define the neurophysiological basis of emotion ascribed an integral role to the peripheral nervous system (James, 1894). From a biological perspective peripheral and central components of the nervous system can be considered a unified, interactive and integrative system, Such an orientation would not only predict but would predicate that peripheral manipulations would affect behavior. Studies in which peripheral manipulations have been shown to influence the behavioral expression of a learned behavior certainly are congruent with this perspective. In fact, it is the detailed analysis provided by these studies which serves to precisely identify the mechanisms by which peripheral hormonal manipulations influence learned behavior that provide the impetus for the paper. In referencing the extensive body of literature on post-trial studies which employed administration of peripheral-acting hormonal treatments to modify learned behavior, the present paper will suggest that post-trial manipulations, like pre-trial biological manipulations, can influence memory indirectly by effects on non-associative variables. By recognizing the potential influence of such indirect effects, serious misinterpretations of post-trial treatment effects, particularly so-called "memory enhancement" effects (Gold and Hall, 1986;
Sternberg et al., 1985) can be circumvented. Studies employing post-trial peripheral hormonal treatments have generally used passive avoidance procedures (McGaugh, 1983; Gold and Hall, 1986). Importantly, results from these studies have revealed a cascade of systemic physiological sequelae that follow the application of the noxious stimulus (Gold and Delanoy, 1981). While a passive avoidance trial is usually defined by the experimenter as ending when exogenous application of the noxious stimulus is terminated and the animal is removed from the test situation, these investigations have drawn attention to the fact that the systemic physiological consequences of noxious stimulation continue for a substantial period of time after the trial. With moderate levels of noxious stimulation, one important long-lasting physiological consequence is related to the release of epinephrine which initiates a sequence of physiological events (e.g. changes in blood glucose) (Cannon, 1927; Gold and Delanoy, 1981). When the level of noxious stimulation is severe, endogenous opiate systems can be activated creating yet another set of distinct neurohumoral sequelae consequent to noxious stimulation (Izquierdo et al., 1986; Martinez Jr., 1986). Post-trial exogenous administration of these hormones, or their pharmacological analogs, appears to simulate the physiological consequences of the noxious stimulation used to induce passive avoidance behavior. The relationship between noxious stimuli and peripheral hormone release to post-trial treatment effects has been most thoroughly detailed for epinephrine and moderate levels of noxious stimulation (Gold and Hall, 1986). In addition to detailing the cascade of physiological events which are initiated by a noxious stimulus, these investigations have shown that post-trial manipulations of stimulation induced physiological events can substantiaUy influence passive avoidance behavior. Generally, post-trial treatment with epinephrine, or other components of the physiological sequence initiated by epinephrine, increases the magnitude of the passive avoidance response when shock intensity is low or moderate (Gold and Delanoy, 1981). Thus, effects of exogenous post-trial epinephrine administration, or related physiological sequelae (Gold, 1986a) (e.g. glucose), can summate
29 with the epinephrine-induced events initiated by noxious stimulation to produce a behavioral effect which is functionally equivalent to increasing the intensity of the noxious stimulus (McCarty and Gold, 1981; Gold et al., 1982). This type of posttrial treatment effect has been interpreted as memory enhancement (Gold and Delanoy, 1981). While authors have been careful to interpret such influences as modulatory in nature, rather than as direct effects on associative mechanisms, the use of terminology such as " m e m o r y enhancement" appears misleading even if used in only a descriptive sense. The problem is that this description focuses attention on only one aspect involved in the analysis of this effect. That is, it emphasizes equivalency of the physical properties of the noxious stimulus (e.g. millamperes of footshock) for the control and treatment groups. Thus, for a given intensity of noxious stimulation one can observe greater passive avoidance behavior in the groups given the post-trial hormonal treatment. Since the noxious stimuli delivered to the control and treated groups are the same, it is concluded that somehow the post-trial treatment enables the animal to better retain this experience which it exhibits by increased passive avoidance behavior. There is an inconsistency, however, in arguing that this increase in passive avoidance behavior represents an appropriate behavioral response to the noxious stimulus. When no post-trial treatments are given and animals display an increase in passive avoidance behavior consequent to an increase in the intensity of the noxious stimulus, this relationship between behavior and the intensity of the noxious stimulus is clearly appropriate and adaptive. When the intensity is held constant, however, and passive avoidance behavior is increased by an exogenous treatment, is this behavioral change also appropriate and adaptive? That is, for a given level of noxious stimulation if a treatment induces an animal to behave as if it received a more intense noxious stimulus than the one actually received, is this an adaptive behavioral response? Indeed, such a behavioral effect induced by posttrial hormonal or pharmacological treatments can be viewed as maladaptive in that it causes the animal to respond to the noxious stimulus as if it were more intense than it actually is. Thus, rather than interpreting changes in performance as indicative of memory enhancement, it could be argued
that hormonal post-trial manipulations induce perceptual distortions. In the reverse situation (i.e. when the noxious stimulus is strong but the treatment produces responding typical for a weak noxious stimulus) it is easy to conclude that the treatment produced a maladaptive behavioral effect. The argument posited here is that when a treatment induces an animal to respond to a weak noxious stimulus as it would to a stronger noxious stimulus, that this effect is also maladaptive and it is inappropriate to characterize such effects in a salutary fashion by labeling them as memory enhancement. That is, responding to a mild noxious stimulus as if it were a strong noxious stimulus is as inappropriate and maladaptive as responding to a strong noxious stimulus as if it were a mild one. The problem with interpreting increases or decreases in passive avoidance behavior induced by an exogenous post-trial treatment as positive or negative effects, is that the referent is the physical intensity of the noxious stimulus (e.g. milliamperes of footshock). If the definition of the noxious stimulus is expanded and viewed as a composite of the physical intensity of the stimulus and its physiological consequences then post-trial hormonal treatments could be considered as either attenuating or enhancing the perceived magnitudes of the noxious stimulus. Thus, in situations where hormonal treatments enhance the physiological cascade induced by the noxious stimulus, an increase in passive avoidance behavior would appear appropriate to the increase in the physiological impact of the noxious stimulus. On the other hand, when the post-trial hormonal manipulation attenuates the physiological consequences of noxious stimulion then a reduction in passive avoidance behavior also seems appropriate. If behavioral performance effects are considered in terms of the relationship of hormonal manipulations to the strength of the noxious stimulus, then the behavior of the animal can be characterized as appropriate and adaptive to the level of the noxious stimulation. Thus, if the behavioral effects of post-trial hormonal treatments are linked to the changes such treatments have on the magnitude of noxious stimulus, there is no need to invoke alterations in memory to account for these effects on behavior. This viewpoint differs substantially from memory-oriented perspectives
30
which consider decreases as behaviorally maladaptive (i.e. memory loss) or increases as superadaprive (i.e. memory enhancement). It can be argued then that post-trial hormonal treatment effects have little relevance for the study of biologically mediated memory but rather are of concern to processes which involve the identification and definition of physiological consequences of the noxious stimulus. The relationship of post-trial hormonal manipulations to memory then is adventitious in that the hormonal manipulations significantly interact with processes initiated by the noxious stimulus which, in the context of a passive avoidance test, happen to be manifested in learned behavior. In conclusion, analysis of the effects of post-trial hormonal manipulations upon passive avoidance behavior indicates that post-trial treatments, like pre-trial treatments, can affect behavioral performance but that such effects are only indirectly related to memory processes. While these observations weaken the case for using post-trial treatments to infer effects upon associative mechanisms, by no means should such precautions be limited to peripheral treatment effects. Further, there is no a priori reason to believe that post-trial central nervous system treatments do not also influence peripheral mechanisms and influence memory processes indirectly. Therefore, it is important to recognize the dynamic interplay between central and peripheral events in the nervous system that was enuciated m a n y years ago in the James-Lange theory of emotion (James, 1894; Cannon, 1927; Schachter and Singer, 1962). Interestingly, the profound effects of peripheral hormone post-trial manipulations upon passive avoidance behavior demonstrated in many recent studies seem to provide new, albeit unintended, support for this long standing peripheral theory of emotion rather than supporting a role for peripheral mechanisms of memory.
Acknowledgements The author wishes to express his gratitude to Dr. M.R. Lynch for her thoughtful suggestions and constructive editing of the manuscript and to Ms. Dawn Doviak for her painstaking efforts in preparation of the manuscript.
References Cannon, W.B. (1927) The James-Lange theory of emotions: a critical examination and an alternate theory, Am. J. Psychol., 39: 106-124. Gold, P.E. (1986a) Glucose modulation of memory storage processing, Behav. Neural Biol., 45: 342-349. Gold, P.E. (1986b) The use of avoidance training in studies of modulation of memory storage, Behav. Neurot. BioL, 46: 87-98. Gold, P.E. and Delanoy, R.L. (1981) ACTH modulations of memory storage processes. In J.L. Martinez Jr., R.A. Jensen, R.B. Messing, H. Rigter and J.L. McGaugh (Eds.), Endogenous Peptides and Learning and Memory Processes, Academic Press, New York, pp. 79-98. Gold, P.E. and Hall, J.L. (1986) Memory enhancement with posttraining glucose injections: possible involvement in epinephrine modulation of memory storage. In H. Matthies (Ed.), Learning and Memory: Mechanisms of Information Storage in the Nervous System, Permagon Press, New York, pp. 307-314. Gold, P.E., McCarty, R. and Sternberg, D.B. (1982) Peripheral catecholamines and memory modulation. In C.A. Marsan and H. Matthies (Eds.), Neuronal Plasticity and Memory Formation, Raven Press, New York, pp. 327-338. Izquierdo, I., Netto, C.A., Chaves, F., Quillfeldt, J., Gianlupi, A. and Oliveira, B. (1986) Role of fl-endorphin and other mechanisms in the simultaneous and consecutive processing of new and old memories. In H. Matthies (Ed.), Learning and Memory: Mechanisms of Information Storage in the Nervous System, Permagon Press, New York, pp, 357-367. James, W. (1984) The physiological basis of emotion, Psychol. Rev., 1: 516-529. Liebman, J.M. (1983) Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology, Neurosci. Biobehav. Rev., 7: 45-72. Martinez Jr., J.L. (1986) Enkephalins are hormonal modulators of learning and memory. In H. Matthies (Edi), Learning and Memory: Mechanisms of Information Storage in the Nervous System. Permagon Press, New York, pp. 373. McCarty, R. and Gold, P.E, (1981) Plasma catecholarmnes: Effects of footshock level and hormonal modulations of memory storage, Hormones Behav., 15: 168-182. McGaugh, J.L. (I983) Hormonal influences on memory, Annu. Rev. Psychol., 34: 297-323. McGaugh, J.L., Liang, K.C. and Intromi, 1.B. (1986) Hormone-transmitter interactions in memory modulation. In H. Matthies (Ed.), Learning and Memory: Mechanisms of Information Storage in the Nervous System, Permagon Press, New York, pp. 305-306. Schachter, S. and Singer, J.E. (1962) Cognitive social and physiological determinants of emotion state, Psychol. Rev., 69: 379-399. Sternberg, D.B., Martinez, J.L., Gold, P.E. and McGaugh, J.L. (1985) Age related memory deficits in rats and mice: enhancement with peripheral injections of epinephrine, Behay. Neural Biol., 44: 213-220.
27
Elsevier NSM 00706
Post-trial hormonal treatment effects: memory modulation or perceptual distortion? R o b e r t J. C a r e y s. U.N. E Health Science Center and V.A. Medical Center, Syracuse, N Y (U.S.A.)
(Received 2 September 1986) (Revised 28 January 1987) (Accepted 30 January 1987)
K e y words: M e m o r y ; H o r m o n e ; Passive a v o i d a n c e ; E p i n e p h r i n e
An extensive literature has developed in recent years demonstrating that a variety of peripheral-acting hormonal and pharmacological treatments, administered in post-trial learning paradigms, can substantially influence memory. Careful analysis of the effects of such treatments in passive avoidance paradigms has provided evidence for an interaction between these treatments and the hormonal and physiological events triggered by the noxious stimulation used to induce passive avoidance behavior. The argument developed in this paper is that such post-trial manipulations distort the relationship between the intensity of the noxious stimulus and its physiological sequelae. Considered in this light, changes in passive avoidance behavior appear to represent perceptual distortions rather than memory effects, per se. That is, rather than interfering or enhancing memory processes, peripheral hormonal treatments may simply produce distortions in the perceived intensity of the noxious stimulus.
A n i m a l learning p a r a d i g m s have been used extensively to investigate biological variables which m a y c o n t r i b u t e to the m e d i a t i o n a n d m o d u l a t i o n of m e m o r y processes. Typically, simple l e a r n i n g s i t u a t i o n s have b e e n e m p l o y e d which involve beh a v i o r a l m o d i f i c a t i o n b y r e w a r d or p u n i s h m e n t contingencies. In these studies biological treatm e n t s have p r o d u c e d a l t e r a t i o n s in b e h a v i o r indicative of interference or i m p r o v e m e n t in m e m o r y function. W h i l e no exogenous p h a r m a c o l o g i c a l o r h o r m o n a l m a n i p u l a t i o n c o u l d be expected to exactly d u p f i c a t e the m y r i a d of s e n s o r y - m o t o r events which constitute the m e m o r y trace o f even the simplest l e a r n e d behavior, a p p l i c a t i o n of biological m a n i p u l a t i o n s to m o d i f y m n e m o n i c processes h a v e b e e n g u i d e d b y the a s s u m p t i o n that storage a n d retrieval processes can be m o d u l a t e d b y o r g a n i s m i c state variables. T h e p r o b l e m has been, however, to t r a n s l a t e effects on b e h a v i o r a l perforCorrespondence: R.J. Carey, Res. and Dev. Serv., V.A. Medical Center, 800 Irving Ave., Syracuse, NY 13210, U.S.A.
m a n c e into direct influences on m e m o r y m e c h a nisms. W h e n the e x p e r i m e n t a l m a n i p u l a t i o n s are p e r f o r m e d either p r i o r to or d u r i n g a l e a r n i n g s i t u a t i o n a n y n u m b e r of o r g a n i s m i c effects of the t r e a t m e n t which are o n l y i n d i r e c t l y related to m e m o r y m a y influence test p e r f o r m a n c e (e.g., alterations in s e n s o r y - m o t o r function, changes in m o t i v a t i o n o r arousal, a n d even m o d i f i c a t i o n s in the efficacy of r e w a r d s a n d p u n i s h m e n t s ) . W h i l e these indirect effects are i n h e r e n t l y interesting in the s t u d y o f the biological s u b s t r a t e s for b e h a v i o r they can c o n f o u n d assessment of direct influences o f the biological t r e a t m e n t s on associative m e c h a nisms. P r o b l e m s involved with i n t e r p r e t i n g perform a n c e effects in terms of p s y c h o l o g i c a l processes are n o t unique to the s t u d y of m e m o r y b u t are a long s t a n d i n g f o r m i d a b l e issue in b r a i n - b e h a v i o r research ( L i e b m a n , 1983). A n a l t e r n a t i v e to a d m i n i s t e r i n g biological treatm e n t s p r i o r to or d u r i n g a l e a r n i n g task is to treat the a n i m a l after the task is p e r f o r m e d . T h e distinct a d v a n t a g e of a p o s t - t r i a l p a r a d i g m is that the
0165-0270/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)
28 effects of a treatment variable can be assessed during subsequent tests when the physiological influences of the treatment have subsided. Using this design, a number of physio-chemical manipulations of brain function have been shown to impair or facilitate subsequent task performance. Interpretations of these findings have often been guided by the facile assumption that post-trial treatment effects are direct effects upon memory mechanisms. In early studies, post-trial effects were observed following experimenter-induced alterations of central nervous system function. More recently, however, a number of reports have shown that post-trial administration of peripherally acting hormonal or pharmacological treatments can substantially influence subsequent test performance (McGaugh, 1983; McGaugh et al., 1986). Certainly, one must consider the possibility of a dynamic interplay between the peripheral and central nervous system. Indeed, the first systematic attempt to define the neurophysiological basis of emotion ascribed an integral role to the peripheral nervous system (James, 1894). From a biological perspective peripheral and central components of the nervous system can be considered a unified, interactive and integrative system, Such an orientation would not only predict but would predicate that peripheral manipulations would affect behavior. Studies in which peripheral manipulations have been shown to influence the behavioral expression of a learned behavior certainly are congruent with this perspective. In fact, it is the detailed analysis provided by these studies which serves to precisely identify the mechanisms by which peripheral hormonal manipulations influence learned behavior that provide the impetus for the paper. In referencing the extensive body of literature on post-trial studies which employed administration of peripheral-acting hormonal treatments to modify learned behavior, the present paper will suggest that post-trial manipulations, like pre-trial biological manipulations, can influence memory indirectly by effects on non-associative variables. By recognizing the potential influence of such indirect effects, serious misinterpretations of post-trial treatment effects, particularly so-called "memory enhancement" effects (Gold and Hall, 1986;
Sternberg et al., 1985) can be circumvented. Studies employing post-trial peripheral hormonal treatments have generally used passive avoidance procedures (McGaugh, 1983; Gold and Hall, 1986). Importantly, results from these studies have revealed a cascade of systemic physiological sequelae that follow the application of the noxious stimulus (Gold and Delanoy, 1981). While a passive avoidance trial is usually defined by the experimenter as ending when exogenous application of the noxious stimulus is terminated and the animal is removed from the test situation, these investigations have drawn attention to the fact that the systemic physiological consequences of noxious stimulation continue for a substantial period of time after the trial. With moderate levels of noxious stimulation, one important long-lasting physiological consequence is related to the release of epinephrine which initiates a sequence of physiological events (e.g. changes in blood glucose) (Cannon, 1927; Gold and Delanoy, 1981). When the level of noxious stimulation is severe, endogenous opiate systems can be activated creating yet another set of distinct neurohumoral sequelae consequent to noxious stimulation (Izquierdo et al., 1986; Martinez Jr., 1986). Post-trial exogenous administration of these hormones, or their pharmacological analogs, appears to simulate the physiological consequences of the noxious stimulation used to induce passive avoidance behavior. The relationship between noxious stimuli and peripheral hormone release to post-trial treatment effects has been most thoroughly detailed for epinephrine and moderate levels of noxious stimulation (Gold and Hall, 1986). In addition to detailing the cascade of physiological events which are initiated by a noxious stimulus, these investigations have shown that post-trial manipulations of stimulation induced physiological events can substantiaUy influence passive avoidance behavior. Generally, post-trial treatment with epinephrine, or other components of the physiological sequence initiated by epinephrine, increases the magnitude of the passive avoidance response when shock intensity is low or moderate (Gold and Delanoy, 1981). Thus, effects of exogenous post-trial epinephrine administration, or related physiological sequelae (Gold, 1986a) (e.g. glucose), can summate
29 with the epinephrine-induced events initiated by noxious stimulation to produce a behavioral effect which is functionally equivalent to increasing the intensity of the noxious stimulus (McCarty and Gold, 1981; Gold et al., 1982). This type of posttrial treatment effect has been interpreted as memory enhancement (Gold and Delanoy, 1981). While authors have been careful to interpret such influences as modulatory in nature, rather than as direct effects on associative mechanisms, the use of terminology such as " m e m o r y enhancement" appears misleading even if used in only a descriptive sense. The problem is that this description focuses attention on only one aspect involved in the analysis of this effect. That is, it emphasizes equivalency of the physical properties of the noxious stimulus (e.g. millamperes of footshock) for the control and treatment groups. Thus, for a given intensity of noxious stimulation one can observe greater passive avoidance behavior in the groups given the post-trial hormonal treatment. Since the noxious stimuli delivered to the control and treated groups are the same, it is concluded that somehow the post-trial treatment enables the animal to better retain this experience which it exhibits by increased passive avoidance behavior. There is an inconsistency, however, in arguing that this increase in passive avoidance behavior represents an appropriate behavioral response to the noxious stimulus. When no post-trial treatments are given and animals display an increase in passive avoidance behavior consequent to an increase in the intensity of the noxious stimulus, this relationship between behavior and the intensity of the noxious stimulus is clearly appropriate and adaptive. When the intensity is held constant, however, and passive avoidance behavior is increased by an exogenous treatment, is this behavioral change also appropriate and adaptive? That is, for a given level of noxious stimulation if a treatment induces an animal to behave as if it received a more intense noxious stimulus than the one actually received, is this an adaptive behavioral response? Indeed, such a behavioral effect induced by posttrial hormonal or pharmacological treatments can be viewed as maladaptive in that it causes the animal to respond to the noxious stimulus as if it were more intense than it actually is. Thus, rather than interpreting changes in performance as indicative of memory enhancement, it could be argued
that hormonal post-trial manipulations induce perceptual distortions. In the reverse situation (i.e. when the noxious stimulus is strong but the treatment produces responding typical for a weak noxious stimulus) it is easy to conclude that the treatment produced a maladaptive behavioral effect. The argument posited here is that when a treatment induces an animal to respond to a weak noxious stimulus as it would to a stronger noxious stimulus, that this effect is also maladaptive and it is inappropriate to characterize such effects in a salutary fashion by labeling them as memory enhancement. That is, responding to a mild noxious stimulus as if it were a strong noxious stimulus is as inappropriate and maladaptive as responding to a strong noxious stimulus as if it were a mild one. The problem with interpreting increases or decreases in passive avoidance behavior induced by an exogenous post-trial treatment as positive or negative effects, is that the referent is the physical intensity of the noxious stimulus (e.g. milliamperes of footshock). If the definition of the noxious stimulus is expanded and viewed as a composite of the physical intensity of the stimulus and its physiological consequences then post-trial hormonal treatments could be considered as either attenuating or enhancing the perceived magnitudes of the noxious stimulus. Thus, in situations where hormonal treatments enhance the physiological cascade induced by the noxious stimulus, an increase in passive avoidance behavior would appear appropriate to the increase in the physiological impact of the noxious stimulus. On the other hand, when the post-trial hormonal manipulation attenuates the physiological consequences of noxious stimulion then a reduction in passive avoidance behavior also seems appropriate. If behavioral performance effects are considered in terms of the relationship of hormonal manipulations to the strength of the noxious stimulus, then the behavior of the animal can be characterized as appropriate and adaptive to the level of the noxious stimulation. Thus, if the behavioral effects of post-trial hormonal treatments are linked to the changes such treatments have on the magnitude of noxious stimulus, there is no need to invoke alterations in memory to account for these effects on behavior. This viewpoint differs substantially from memory-oriented perspectives
30
which consider decreases as behaviorally maladaptive (i.e. memory loss) or increases as superadaprive (i.e. memory enhancement). It can be argued then that post-trial hormonal treatment effects have little relevance for the study of biologically mediated memory but rather are of concern to processes which involve the identification and definition of physiological consequences of the noxious stimulus. The relationship of post-trial hormonal manipulations to memory then is adventitious in that the hormonal manipulations significantly interact with processes initiated by the noxious stimulus which, in the context of a passive avoidance test, happen to be manifested in learned behavior. In conclusion, analysis of the effects of post-trial hormonal manipulations upon passive avoidance behavior indicates that post-trial treatments, like pre-trial treatments, can affect behavioral performance but that such effects are only indirectly related to memory processes. While these observations weaken the case for using post-trial treatments to infer effects upon associative mechanisms, by no means should such precautions be limited to peripheral treatment effects. Further, there is no a priori reason to believe that post-trial central nervous system treatments do not also influence peripheral mechanisms and influence memory processes indirectly. Therefore, it is important to recognize the dynamic interplay between central and peripheral events in the nervous system that was enuciated m a n y years ago in the James-Lange theory of emotion (James, 1894; Cannon, 1927; Schachter and Singer, 1962). Interestingly, the profound effects of peripheral hormone post-trial manipulations upon passive avoidance behavior demonstrated in many recent studies seem to provide new, albeit unintended, support for this long standing peripheral theory of emotion rather than supporting a role for peripheral mechanisms of memory.
Acknowledgements The author wishes to express his gratitude to Dr. M.R. Lynch for her thoughtful suggestions and constructive editing of the manuscript and to Ms. Dawn Doviak for her painstaking efforts in preparation of the manuscript.
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