Medical Hypotheses 4: 403-410, 1978.
ATTENUATING EFFECT OF FIGHTING ON SHOCK-INDUCED GASTRIC HYPOTHESIS OF INHIBITION ULCERATION AND HYPERTENSION: BY SENSORY FEEDBACK A. R. Mawson. City College, Loyola University, New Orleans, Louisiana 70118, USA. ABSTRACT A behavioral-biochemical hypothesis is presented to explain the attenuating effect of fighting on electric-shock induced gastric ulceration and hypertension in rats. It is suggested that shock-induced gastric lesions and hypertension result from undampened oscillations in central cholinergic and adrenergic activity, respectively, and that the sensory input derived from fighting serves to reduce the amplitude of these oscillations via a process of inhibition. The hypothesis suggests that other forms of sensory input in addition to that supplied by fighting - whether self-generated or produced artificially by electrical or mechanical stimulators - would have an identical equilibrating effect on oscillations in neurotransmitter activity. INTRODUCTION Weiss -et al. (1) have shown that rats subjected to electric shock and allowed to fight with each other or to engage in aggressive displays, develop less severe gastric lesions in response to the shock than rats that are shocked alone and unable to fight. To explain this observation, the authors first raised the possibility that fighting served as a "coping response". Noting the circularity of this argument, it was then suggested that fighting reduced gastric lesions as a result of providing feedback that was psychologically "relevant" to the animals in one of three possible ways. First, since the duration of fighting (2 set) coincided with the duration of the shocks, the animals may have associated their fighting with shock-termination, and this may in some way have reduced the severity of the lesions. Secondly, fighting may have distracted the animals from awareness of the shocks. Thirdly, it was suggested that "certain highly prepotent responses in danger situations, such as fighting, might inherently produce their own relevant feedback" (1, p. 258). Additional data were not presented to support any of these hypotheses.
403
An alternative, behavioral-biochemical explanation is proposed here, which rests on four partially-established empirical generalizations: (a) Electric shock elicits varying degrees of central adrenergic arousal (2), depending on the intensity of the shock, together with the inhibition of gastric mucosal blood flow and acid secretion (3), which is then followed by a proportionately intense compensatory ("rebound") increase in cholinergic activation (4-7). (b) Gastric ulceration occurs following shock termination (8), during the rebound cholinergic-activation phase (5,6), at a time when gastric mucosal blood flow and acid secretion are presumably increased. (c) The greater the initial increase in adrenergic arousal, the greater the amplitude of the rebound increase in cholinergic arousal, and the greater the likelihood and extent of ulceration (5,6). (d) Continued electric shock elicits a rebound increase in adrenergic activation, which is proportional to the prior degree of cholinergic activation (cf. 9). INHIBITION BY SENSORY FEEDBACK Assuming that oscillations in adrenergic and cholinergic activity are normally kept within fairly narrow limits, the hypothesis proposed for consideration is that this equilibrium is maintained, in part, by sensory feedback generated by the organism's own behavior. The hypothesis states that: (i) Whenever there is an imbalance between neurotransmitter systems in favor of adrenergic dominance (resulting from endogenous factors, external stress, e.g., electric shock, or both), locomotor and/or motivational behavior is elicited which is proportional in intensity to the degree of adrenergic activation (5,6,10). Any such response is described as stimulation-seeking behavior (SSB). The concept of SSB, and the notion that organisms have a physiological need for stimulation over and above the needs for specific nutrients, originally arose from experiments begun in the early 1950s indicating that laboratory animals and humans could be motivated to work for rewards other than conventional reinforcers (e.g.,food, water, sex), and that actual neurophysiological deficits resulted from prolonged sensory restriction (11-14).
404
As defined here, SSB is any response that enhances or facilitates contact between an organism's sensory receptors and external objects or surfaces. All forms of locomotor activity, including fighting, would thus be considered stiSSB also embraces the peripheral mulation-seeking behavior. autonomic changes which occur in states of intense behavioral excitation, including piloerection, increased sweating and skin conductance, and dilatation of the pupils and nostrils, all of which may serve to facilitate increases in the rate and quantity of stimulation. (ii) The sensory input derived from SSB is fed back into the C.N.S. where it activates cholinergic neurons. No direct evidence in support of this statement exists at present. However, it may be noted that high concentrations of cholinergic neurons are found in the septum and hippocampus (15-171, and that these structures are responsive to changes in sensory input (18). (iii) Cholinergic neurons in turn inhibit adrenergic neurons (cf. 191, thereby dampening the level of adrenergic arousal elicited by the original stumulus. In support of this aspect of the hypothesis, evidence has been reported (20) suggesting that acetlycholine is an inhibitory transmitter in the lateral hypothalamus, an area known to contain moderate concentrations of adrenergic neurons (21). Direct stimulation of the ventromedial hypothalamus, parts of which contain acetylcholine (191, inhibits lateral hypothalamic activity (22). Electrophysiological findings demonstrate the existence of afferent projections from the acetylcholine-containing septum and hippocampus to hypothalamic neurons (23). Areas including the septohippocampal region are also known to exert inhibitory effects on structures which, when stimulated electrically, elicit increased adrenergic activity (4,24-27, cf. 28). The latter observations can be explained in terms of a cholinergically-induced inhibition of adrenergic neurons. The novel aspect of the hypothesis is that the cholinergic inhibitory mechanism is activated, in part, by behaviorgenerated increased in sensory input. The greater the degree of adrenergic arousal, the greater the quantity of input needed to activate the inhibitory mechanism and restore neurotransmitter balance. Hence, the greater the intensity of SSB - which can take the form of licking, sucking, eating, drinking, and gnawing, at low levels, to agitation, aggression, running, and vigorous selfmutilation, at progressively higher levels. While the sensorimotor part of the hypothesized inhibitory feedback loop awaits investigation, the work of Stolk et al. (2) provides indirect support for the proposal that the level -
405
of adrenergic arousal elicited by various stimuli can be reduced by behavior-generated increases in stimulation. They found that rats receiving footshocks without a partner, and thus unable to fight, had an increased turnover of norpinephrine in the medulla-pons during the period of shock, whereas rats that were shocked in pairs and engaged in fighting showed no such alteration in regional norepinephrine metabolism during the shock procedure. IMPLICATIONS If the level of shock-induced adrenergic arousal is reduced by fighting, and points (a) and (b) above, are correct, then the above-mentioned finding of Weiss et al. (1) can be explained as follows. The sensory input derived from fighting reduces the level of adrenergic arousal via the activation of cholinergic neurons; hence, the subsequent rebound increase in cholinergic activation is also reduced, with a concomitant decrease in the probability and extent of gastric ulceration (see Fig. 1). Conversely, the hypothesis predicts that if the organism is subjected to shock and is either unable to move or restricted in its movements, the absence of behavior-generated increases in stimulation would be expected to lead to undampened increases in adrenergic arousal, followed by intense cholinergic rebound activity. This could explain the occurrence of gastric lesions in animals that were shocked alone and unable to fight (11, and the general phenomenon of immobilization-induced gastric ulceration (29). Moreover, assuming that the peak period of locomotor activity coincides with the peak level of adrenergic activation, Ader's (29) observation that animals immobilized during the period of greatest activity develop more severe lesions than animals immobilized when normally inactive might also be explained in terms of an intense cholinergic rebound following the initially high level of adrenergic activation.
406
It has been suggested that SSB is part of an inhibitory feedback loop which serves to dampen both central and peripheral In addition oscillations in adrenergic and cholinergic activity. to the cholinergic effects described above, the hypothesis further predicts that if the organism is unable to obtain sensory input, undampened rebound increases in adrenergic arousal would also be expected to occur (point (a)), resulting in periods of high blood pressure and other symptoms of sympathetic nervous system 6;veractivation. In accordance with this corollary hypothesis, Kunz et al. (30) reported that rats tested in isolation and unable to make aggressive (i.e., stimulation-seeking) responses became chronically hypertensive when subjected to footshock over a period of seven days, whereas hypertension did not develop in rats that were shocked in pairs and allowed to fight with each other (see Fig. 1).
hypertension
Adrenergic Arousal
Cholinergic Arousal
Time
-
Fig. 1 Schematic representation of the hypothesized relationship between electric shock, fighting, and time-dependent alterations in adrenergiccholinergic activity. A. Effect of shock in the absence of actual or display fighting; B. Homeostatic effect of fighting on the neurochemical response to electric shock.
407
CONCLUSION It is proposed that shock-induced hypertension and gastric lesions result from undampened oscillations in adrenergic and Observations indicating cholinergic activity, respectively. that fighting serves to attenuate these effects are tentatively explained in terms of the hypothesis of inhibition by sensory feedback. According to this hypothesis, fighting is a form of The sensory input thus obtained stimulation-seeking behavior. activates central cholinergic neurons. These neurons in turn dampen the level of adrenergic arousal elicited by electric shock. The amplitude of the subsequent rebound oscillations in both adrenergic and cholinergic activity are thereby reduced, together with their associated visceral and autonomic effects. The hypothesis suggests that other forms of stimulation apart from that derived from fighting would have an identical equilibratory effect on neurotransmitter activity. To test this idea, a modified version of Weiss et al. 's (1) experimental procedure coul Instead of allowing the animals to obtain stimulabe utilized. tion by vigorous bodily movement, including fighting, mild electrical or mechanical stimulation could be given concurrently with, or immediately following , the administration of shocks. If this proved to be effective in-reducing ulceration and hypertension, a rational basis would be provided for the development of artificial stimulators for therapeutic purposes. REFERENCES 1.
2.
3. 4. 5.
Weiss JM, Pohorecky LA, Salman J, Gruenthal M. Attenuation of gastric lesions by psychological aspects of aggression in rats. J. Comp. Physiol. Psychol. 90: 252, 1976. Stolk JM, Connor RL, Levine S, Barchas JD. Brain norepinephrine metabolism and shock-induced fighting behavior in rats: differential effects of shock and fighting on the neurochemical response to a common footshock stimulus. J. Pharmacol. Exp. Therap. 190: 193, 1974. Osumi Y, Aibara S, Sakal I(, Fujiwara M. Central noradrenergic inhibition of gastric mucosal blood flow and acid secretion in rats. Life Sci. 20: 1407, 1977. Gellhorn E. Principles of Autonomic-Somatic Integrations. University of Minnesota Press, Minneapolis, 1967. Anisman H. Time-dependent variations in aversively motivated behaviors: nonassociative effects of cholinergic and catecholaminergic activity. Psychol. Rev. 82: 359, 1975.
408
6.
7.
8. 9. 10.
11.
12. 13. 14. 15. 16. 17.
18. 19.
20.
Anisman H. Neurochemical changes elicited by stress: behavioral correlates, in Psychopharmacology of Aversively Motivated Behavior (H. Anisman, G. Bignami, eds) Plenum Press, New York, 1977. Zajaczkowska MN. Acetylcholine content in the central and peripheral nervous system and its synthesis the rat brain during stress and post-stress exhaustion. Acta Physiol. Pol. 26: 493, 1975. Desiderato 0, MacKinnon JR, Hissom H. Development of gastric lesions in rats following stress termination. J. Comp. Physiol. Psychol. 87: 208, 1974. Fibiger HC, Lynch GS, Cooper HP. A biphasic action of central cholinergic stimulation on behavioral arousal in the rat. Psychopharmacologia 20: 366, 1971. Reis DJ, Fuxe K. Brain norepinephrine: evidence that neuronal release is essential for sham rage behavior following brainstem transection in cat. Proc. Nat. Acad. Sci. 64: 108, 1969. Zubek JP, ed. Sensory Deprivation: Fifteen Years of Research. Appleton-Century-Crofts, New York, 1969. Montagu A. Touching: The Human Significance of the Skin. Harper and Row, New York, 1972. Zuckerman M. The sensation-seeking motive. p. 80 in Progress in Experimental Personality Research, Vol. 7 (BA Maher, ed) Academic Press, New York, 1974. Riesen AH, ed. The Developmental Neuropsychology of Sensory Deprivation. Academic Press, New York, 1975. Shute CCD, Lewis PR. The ascending cholinergic reticular system: neocortical, olfactory and sub-cortical projections. Brain 90: 497, 1967. Bland BH, Kostopoulos GK, Phillips JW. Acetylcholine sensitivity of hippocampal formation neurons. Can. J. Physiol. Pharmacol. 52: 966, 1974. Dudar JD. The role of septal nuclei in the release of acetylcholine from the rabbit cerebral cortex and dorsal hippocampus and the effect of atropine. Brain Res. 129: 237, 1977. Segal J. Sensory convergence in the hippocampal system. J. Comp. Physiol. Psychol. 87: 91, 1974. Margules DL, Margules AS. The development of operant responses by noradrenergic activation and cholinergic suppression of movements. p. 203 in Efferent Organization and the Integration of Behavior (JD Maser, ed) Academic Press, New York, 1973. Oomura Y, Ono T, Sugimori M, Wayner MJ. Acetylcholine, an inhibitory transmitter in the rat lateral hypothalamus. Brain Res. Bull. 1: 151, 1976.
409
21. 22.
23.
24. 25.
26. 27. 28.
29.
30.
Fuxe K. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol. Stand. 64: (Suppl. 247) 37, 1965 Oomura Y, Ooyama H, Yamamoto T, Naka F. Reciprocal relationship of the lateral and ventromedial hypothalamus in the regulation cf food intake. Physiol. Behav. 2: 97, 1967. Dalith M, Conforti N, Feldman S. Electrophpsiological studies of hippocampal, septal and midbrain projections to the hypothalamus of the rat. Arch. Int. Physiol. Biochim. 82: 7, 1974. Jarrard LE. The hippocampus and motivation. Psychol. Bull. 79: 1, 1973. Miller JJ, Mogenson GJ. Modulatory influences of the septum on lateral hypothalamic self-stimulation. Exp. Neurol. 33: 671, 1971. Altman J, Brunner RL, Bayer SA. The hippocampus and behavioral maturation. Behav. Biol. 8: 557, 1973. Isaacson RL. The Limbic System. Plenum Press, New York, 1974. Nadel L, O'Keefe J, Black A. Slam on the brakes: a critique of Altman, Brunner, & Bayer's response-inhibition model of hippocampal function. Behav. Biol. 14: 151, 1975. Ader R. Experimentally induced gastric lesions. Results and implications of studies in animals, in Duodenal Ulcer. Advances in Psychosomatic Medicine, Vol. 6 (H. Weiner, ed) S. Karger, Basel, 1971. Kunz E, Vallette N, Laborit H. R81e de l'apprentissage dans le me'canisme d'inhibition comportementale et de l'hypertension art&ielle consecutives & l'application de stimulus aversifs sans possibilitede fuite or de lutte. Agressologie 15: 381, 1974.
410
ATTENUATING EFFECT OF FIGHTING ON SHOCK-INDUCED GASTRIC HYPOTHESIS OF INHIBITION ULCERATION AND HYPERTENSION: BY SENSORY FEEDBACK A. R. Mawson. City College, Loyola University, New Orleans, Louisiana 70118, USA. ABSTRACT A behavioral-biochemical hypothesis is presented to explain the attenuating effect of fighting on electric-shock induced gastric ulceration and hypertension in rats. It is suggested that shock-induced gastric lesions and hypertension result from undampened oscillations in central cholinergic and adrenergic activity, respectively, and that the sensory input derived from fighting serves to reduce the amplitude of these oscillations via a process of inhibition. The hypothesis suggests that other forms of sensory input in addition to that supplied by fighting - whether self-generated or produced artificially by electrical or mechanical stimulators - would have an identical equilibrating effect on oscillations in neurotransmitter activity. INTRODUCTION Weiss -et al. (1) have shown that rats subjected to electric shock and allowed to fight with each other or to engage in aggressive displays, develop less severe gastric lesions in response to the shock than rats that are shocked alone and unable to fight. To explain this observation, the authors first raised the possibility that fighting served as a "coping response". Noting the circularity of this argument, it was then suggested that fighting reduced gastric lesions as a result of providing feedback that was psychologically "relevant" to the animals in one of three possible ways. First, since the duration of fighting (2 set) coincided with the duration of the shocks, the animals may have associated their fighting with shock-termination, and this may in some way have reduced the severity of the lesions. Secondly, fighting may have distracted the animals from awareness of the shocks. Thirdly, it was suggested that "certain highly prepotent responses in danger situations, such as fighting, might inherently produce their own relevant feedback" (1, p. 258). Additional data were not presented to support any of these hypotheses.
403
An alternative, behavioral-biochemical explanation is proposed here, which rests on four partially-established empirical generalizations: (a) Electric shock elicits varying degrees of central adrenergic arousal (2), depending on the intensity of the shock, together with the inhibition of gastric mucosal blood flow and acid secretion (3), which is then followed by a proportionately intense compensatory ("rebound") increase in cholinergic activation (4-7). (b) Gastric ulceration occurs following shock termination (8), during the rebound cholinergic-activation phase (5,6), at a time when gastric mucosal blood flow and acid secretion are presumably increased. (c) The greater the initial increase in adrenergic arousal, the greater the amplitude of the rebound increase in cholinergic arousal, and the greater the likelihood and extent of ulceration (5,6). (d) Continued electric shock elicits a rebound increase in adrenergic activation, which is proportional to the prior degree of cholinergic activation (cf. 9). INHIBITION BY SENSORY FEEDBACK Assuming that oscillations in adrenergic and cholinergic activity are normally kept within fairly narrow limits, the hypothesis proposed for consideration is that this equilibrium is maintained, in part, by sensory feedback generated by the organism's own behavior. The hypothesis states that: (i) Whenever there is an imbalance between neurotransmitter systems in favor of adrenergic dominance (resulting from endogenous factors, external stress, e.g., electric shock, or both), locomotor and/or motivational behavior is elicited which is proportional in intensity to the degree of adrenergic activation (5,6,10). Any such response is described as stimulation-seeking behavior (SSB). The concept of SSB, and the notion that organisms have a physiological need for stimulation over and above the needs for specific nutrients, originally arose from experiments begun in the early 1950s indicating that laboratory animals and humans could be motivated to work for rewards other than conventional reinforcers (e.g.,food, water, sex), and that actual neurophysiological deficits resulted from prolonged sensory restriction (11-14).
404
As defined here, SSB is any response that enhances or facilitates contact between an organism's sensory receptors and external objects or surfaces. All forms of locomotor activity, including fighting, would thus be considered stiSSB also embraces the peripheral mulation-seeking behavior. autonomic changes which occur in states of intense behavioral excitation, including piloerection, increased sweating and skin conductance, and dilatation of the pupils and nostrils, all of which may serve to facilitate increases in the rate and quantity of stimulation. (ii) The sensory input derived from SSB is fed back into the C.N.S. where it activates cholinergic neurons. No direct evidence in support of this statement exists at present. However, it may be noted that high concentrations of cholinergic neurons are found in the septum and hippocampus (15-171, and that these structures are responsive to changes in sensory input (18). (iii) Cholinergic neurons in turn inhibit adrenergic neurons (cf. 191, thereby dampening the level of adrenergic arousal elicited by the original stumulus. In support of this aspect of the hypothesis, evidence has been reported (20) suggesting that acetlycholine is an inhibitory transmitter in the lateral hypothalamus, an area known to contain moderate concentrations of adrenergic neurons (21). Direct stimulation of the ventromedial hypothalamus, parts of which contain acetylcholine (191, inhibits lateral hypothalamic activity (22). Electrophysiological findings demonstrate the existence of afferent projections from the acetylcholine-containing septum and hippocampus to hypothalamic neurons (23). Areas including the septohippocampal region are also known to exert inhibitory effects on structures which, when stimulated electrically, elicit increased adrenergic activity (4,24-27, cf. 28). The latter observations can be explained in terms of a cholinergically-induced inhibition of adrenergic neurons. The novel aspect of the hypothesis is that the cholinergic inhibitory mechanism is activated, in part, by behaviorgenerated increased in sensory input. The greater the degree of adrenergic arousal, the greater the quantity of input needed to activate the inhibitory mechanism and restore neurotransmitter balance. Hence, the greater the intensity of SSB - which can take the form of licking, sucking, eating, drinking, and gnawing, at low levels, to agitation, aggression, running, and vigorous selfmutilation, at progressively higher levels. While the sensorimotor part of the hypothesized inhibitory feedback loop awaits investigation, the work of Stolk et al. (2) provides indirect support for the proposal that the level -
405
of adrenergic arousal elicited by various stimuli can be reduced by behavior-generated increases in stimulation. They found that rats receiving footshocks without a partner, and thus unable to fight, had an increased turnover of norpinephrine in the medulla-pons during the period of shock, whereas rats that were shocked in pairs and engaged in fighting showed no such alteration in regional norepinephrine metabolism during the shock procedure. IMPLICATIONS If the level of shock-induced adrenergic arousal is reduced by fighting, and points (a) and (b) above, are correct, then the above-mentioned finding of Weiss et al. (1) can be explained as follows. The sensory input derived from fighting reduces the level of adrenergic arousal via the activation of cholinergic neurons; hence, the subsequent rebound increase in cholinergic activation is also reduced, with a concomitant decrease in the probability and extent of gastric ulceration (see Fig. 1). Conversely, the hypothesis predicts that if the organism is subjected to shock and is either unable to move or restricted in its movements, the absence of behavior-generated increases in stimulation would be expected to lead to undampened increases in adrenergic arousal, followed by intense cholinergic rebound activity. This could explain the occurrence of gastric lesions in animals that were shocked alone and unable to fight (11, and the general phenomenon of immobilization-induced gastric ulceration (29). Moreover, assuming that the peak period of locomotor activity coincides with the peak level of adrenergic activation, Ader's (29) observation that animals immobilized during the period of greatest activity develop more severe lesions than animals immobilized when normally inactive might also be explained in terms of an intense cholinergic rebound following the initially high level of adrenergic activation.
406
It has been suggested that SSB is part of an inhibitory feedback loop which serves to dampen both central and peripheral In addition oscillations in adrenergic and cholinergic activity. to the cholinergic effects described above, the hypothesis further predicts that if the organism is unable to obtain sensory input, undampened rebound increases in adrenergic arousal would also be expected to occur (point (a)), resulting in periods of high blood pressure and other symptoms of sympathetic nervous system 6;veractivation. In accordance with this corollary hypothesis, Kunz et al. (30) reported that rats tested in isolation and unable to make aggressive (i.e., stimulation-seeking) responses became chronically hypertensive when subjected to footshock over a period of seven days, whereas hypertension did not develop in rats that were shocked in pairs and allowed to fight with each other (see Fig. 1).
hypertension
Adrenergic Arousal
Cholinergic Arousal
Time
-
Fig. 1 Schematic representation of the hypothesized relationship between electric shock, fighting, and time-dependent alterations in adrenergiccholinergic activity. A. Effect of shock in the absence of actual or display fighting; B. Homeostatic effect of fighting on the neurochemical response to electric shock.
407
CONCLUSION It is proposed that shock-induced hypertension and gastric lesions result from undampened oscillations in adrenergic and Observations indicating cholinergic activity, respectively. that fighting serves to attenuate these effects are tentatively explained in terms of the hypothesis of inhibition by sensory feedback. According to this hypothesis, fighting is a form of The sensory input thus obtained stimulation-seeking behavior. activates central cholinergic neurons. These neurons in turn dampen the level of adrenergic arousal elicited by electric shock. The amplitude of the subsequent rebound oscillations in both adrenergic and cholinergic activity are thereby reduced, together with their associated visceral and autonomic effects. The hypothesis suggests that other forms of stimulation apart from that derived from fighting would have an identical equilibratory effect on neurotransmitter activity. To test this idea, a modified version of Weiss et al. 's (1) experimental procedure coul Instead of allowing the animals to obtain stimulabe utilized. tion by vigorous bodily movement, including fighting, mild electrical or mechanical stimulation could be given concurrently with, or immediately following , the administration of shocks. If this proved to be effective in-reducing ulceration and hypertension, a rational basis would be provided for the development of artificial stimulators for therapeutic purposes. REFERENCES 1.
2.
3. 4. 5.
Weiss JM, Pohorecky LA, Salman J, Gruenthal M. Attenuation of gastric lesions by psychological aspects of aggression in rats. J. Comp. Physiol. Psychol. 90: 252, 1976. Stolk JM, Connor RL, Levine S, Barchas JD. Brain norepinephrine metabolism and shock-induced fighting behavior in rats: differential effects of shock and fighting on the neurochemical response to a common footshock stimulus. J. Pharmacol. Exp. Therap. 190: 193, 1974. Osumi Y, Aibara S, Sakal I(, Fujiwara M. Central noradrenergic inhibition of gastric mucosal blood flow and acid secretion in rats. Life Sci. 20: 1407, 1977. Gellhorn E. Principles of Autonomic-Somatic Integrations. University of Minnesota Press, Minneapolis, 1967. Anisman H. Time-dependent variations in aversively motivated behaviors: nonassociative effects of cholinergic and catecholaminergic activity. Psychol. Rev. 82: 359, 1975.
408
6.
7.
8. 9. 10.
11.
12. 13. 14. 15. 16. 17.
18. 19.
20.
Anisman H. Neurochemical changes elicited by stress: behavioral correlates, in Psychopharmacology of Aversively Motivated Behavior (H. Anisman, G. Bignami, eds) Plenum Press, New York, 1977. Zajaczkowska MN. Acetylcholine content in the central and peripheral nervous system and its synthesis the rat brain during stress and post-stress exhaustion. Acta Physiol. Pol. 26: 493, 1975. Desiderato 0, MacKinnon JR, Hissom H. Development of gastric lesions in rats following stress termination. J. Comp. Physiol. Psychol. 87: 208, 1974. Fibiger HC, Lynch GS, Cooper HP. A biphasic action of central cholinergic stimulation on behavioral arousal in the rat. Psychopharmacologia 20: 366, 1971. Reis DJ, Fuxe K. Brain norepinephrine: evidence that neuronal release is essential for sham rage behavior following brainstem transection in cat. Proc. Nat. Acad. Sci. 64: 108, 1969. Zubek JP, ed. Sensory Deprivation: Fifteen Years of Research. Appleton-Century-Crofts, New York, 1969. Montagu A. Touching: The Human Significance of the Skin. Harper and Row, New York, 1972. Zuckerman M. The sensation-seeking motive. p. 80 in Progress in Experimental Personality Research, Vol. 7 (BA Maher, ed) Academic Press, New York, 1974. Riesen AH, ed. The Developmental Neuropsychology of Sensory Deprivation. Academic Press, New York, 1975. Shute CCD, Lewis PR. The ascending cholinergic reticular system: neocortical, olfactory and sub-cortical projections. Brain 90: 497, 1967. Bland BH, Kostopoulos GK, Phillips JW. Acetylcholine sensitivity of hippocampal formation neurons. Can. J. Physiol. Pharmacol. 52: 966, 1974. Dudar JD. The role of septal nuclei in the release of acetylcholine from the rabbit cerebral cortex and dorsal hippocampus and the effect of atropine. Brain Res. 129: 237, 1977. Segal J. Sensory convergence in the hippocampal system. J. Comp. Physiol. Psychol. 87: 91, 1974. Margules DL, Margules AS. The development of operant responses by noradrenergic activation and cholinergic suppression of movements. p. 203 in Efferent Organization and the Integration of Behavior (JD Maser, ed) Academic Press, New York, 1973. Oomura Y, Ono T, Sugimori M, Wayner MJ. Acetylcholine, an inhibitory transmitter in the rat lateral hypothalamus. Brain Res. Bull. 1: 151, 1976.
409
21. 22.
23.
24. 25.
26. 27. 28.
29.
30.
Fuxe K. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol. Stand. 64: (Suppl. 247) 37, 1965 Oomura Y, Ooyama H, Yamamoto T, Naka F. Reciprocal relationship of the lateral and ventromedial hypothalamus in the regulation cf food intake. Physiol. Behav. 2: 97, 1967. Dalith M, Conforti N, Feldman S. Electrophpsiological studies of hippocampal, septal and midbrain projections to the hypothalamus of the rat. Arch. Int. Physiol. Biochim. 82: 7, 1974. Jarrard LE. The hippocampus and motivation. Psychol. Bull. 79: 1, 1973. Miller JJ, Mogenson GJ. Modulatory influences of the septum on lateral hypothalamic self-stimulation. Exp. Neurol. 33: 671, 1971. Altman J, Brunner RL, Bayer SA. The hippocampus and behavioral maturation. Behav. Biol. 8: 557, 1973. Isaacson RL. The Limbic System. Plenum Press, New York, 1974. Nadel L, O'Keefe J, Black A. Slam on the brakes: a critique of Altman, Brunner, & Bayer's response-inhibition model of hippocampal function. Behav. Biol. 14: 151, 1975. Ader R. Experimentally induced gastric lesions. Results and implications of studies in animals, in Duodenal Ulcer. Advances in Psychosomatic Medicine, Vol. 6 (H. Weiner, ed) S. Karger, Basel, 1971. Kunz E, Vallette N, Laborit H. R81e de l'apprentissage dans le me'canisme d'inhibition comportementale et de l'hypertension art&ielle consecutives & l'application de stimulus aversifs sans possibilitede fuite or de lutte. Agressologie 15: 381, 1974.
410
