Psychological Reports, 1975, 37, 1079-1084. @ Psychological Reports 1975 HIPPOCAMPAL LESIONS AND PERFORMANCE ON A GEOMETRIC PROGRESSIVE R A T I O SCHEDULE W.
9. STEWART
AND N. M. BLAMPIEDa
Canterbury, Christchurch, N. Z.
Univer~ityof
Summary.-Previous research has frequently reported that hippocampally lesioned rats perseverate. On a geometric progressive ratio schedule, i n which reinforcement contingencies became gradually more adverse, rats with dorsal or ventral hippocampal lesions did not perseverate more than cortically lesioned or unoperated controls (ns = 7, 8 ) . There was a significant reduction in the number of responses pea session over the 10 experimental days, for all groups. Animals with lesions of the hippocampus are frequently said to perseverare (Douglas, 1 9 6 7 ) , i.e., they continue to exhibit non-adaptive patterns of behaviour which non-lesioned animals either d o not emit at all or rapidly cease to emit. And, lesioned animals continue to respond longer in t h e face of adverse experimental conditions. O n simple fixed ratio schedules, hippocampally lesioned subjects respond more rapidly than control subjects (Rabe & Haddad, 1968). W h e n exposed to a succession of increasing fixed ratio schedules (successive ratio) hippocampally lesioned subjects have also been found to respond at higher rates than controls o n some of the ratio schedules (Ehrlich, 1963; Schmaltz, Wolf, & Trejo, 1973). Carey ( 1969), however, found no difference between hippocampally lesioned and control subjects o n a successive ratio schedule. T o date, the effect of hippocampal lesions on performance on a true progressive ratio schedule, in which the number of responses required for reinforcement increases systematically following each reinforcement, has not been reported, although such a schedule would seem to provide an appropriate test of the perseveration hypothesis since it confronts the animal with increasingly adverse conditions of reinforcement, but without abrupt changes in reinforcemenc density or character (Findley, 1958). Since arithmetic progressions approximate to fixed ratios at high values, a geometric progression was used in the present study. Because of evidence that dorsal and ventral hippocampal lesions may have different behavioral effects (Nadel, 1968) lesions were distributed within the hippocampus.
METHOD Subjectr Twenty-eight rats (Otago-N. Z. Black-White strain), 120 to 200 days old, 'Now at La Trobe University, Victoria, Australia. 'Address reprint requests to N. M. Blampied. Research supported by Grants C70/20, 70/44, 72/24, and 73/2/34 to N. M. B. Research reported was performed in partial fulfillment of the requirement of the M.Sc. degree by W.J.S.
1080
W. J. STEWART & N. M. BLAMPIED
were used. They were housed individually and kept at 80% of their free-feeding weight for the duration of the experiment except for a few days pre- and postoperatively. Twenty-one animals were lesioned; 6 in the neocortex (males), seven in the ventral hippocampus ( 1 female, 6 males) and 8 in the dorsal hippocampus ( 7 males, 1 female). The other 7 racs ( 5 females, 2 males) served as unoperated controls.
Apparatus A standard Grason-Stadler rat Skinner box, enclosed in a sound-attenuating chest with an exhaust fan which masked external noise, was used. It was illuminated by a fluorescent strip mounted 12 cm above the Skinner box. The Skinner box contained a single bar mounted to the right of a central dipper hole through which liquid food (milk enriched with 'Complan') could be delivered 0.05 ml at a time. Programming of reinforcements was carried out by standard electro-mechanical devices. Reinforcements were scheduled by a Gerbrands Ratio Programmer. Following premedication with acetyl-promazine and atropine sulphate injected intramuscularly, animals were anesthetized with chloral hydrate (350 mg/kg). Bilateral electrolytic lesions were produced srereotaxically by passing 3-mA anodal current for 10 sec. through a stainless steel, acrylic-insulated electrode. The cathode was moistened with saline and attached to the tail. Coordinates were taken from the Pellegrino and Cushman (1967) atlas and were as follows: anterior-posterior: -4.0 mm; lateral: 3.0 mm (all groups); depth: 1.5 mm neocortical; 3.0 mm dorsal hippocampus; 7.5 mm ventral hippocampus. The electrode was angled at 20' from the vertical for the dorsal and ventral hippocampal lesions.
Histology The lesioned rats were sacrificed with an overdose of sodium pentobarbital and perfused with saline and formalin. The extracted brains were left in formalin solution for 15 days then sectioned at 100-150r. Sections were mounted, stained with thioin and examined under a microscope. Several subjects had to be reassigned to different groups. Three racs in the dorsal hippocampal group suffered damage to the thalamus and were grouped separately in subsequent analysis. One ventral hippocampal subject suffered thalamic damage - and its results were discarded. The maximum and minimum damage to the various regions are shown in Fig. 1. The most extensive neocortical lesions extended slightly into the dorsal hippocampus; while the largest ventral hippocampal lesions extended into the entorhinal cortex.
HIPPOCAMPAL LESIONS AND PROGRESSIVE RATIO SCHEDULE
1081
FIG. 1 Reconstructions of the largest and smallest lesions found in the animals 1esioned in the neo-cortex, dorsal hippocampus, and ventral hippocampus (from Pellegrino & Cushman, 1967) Proced~~e Following deprivation, and adaptation to the Skinner box subjects were trained to bar-press by successive approximation. They were then given one session of 80 continuous reinforcements. Lesion-group subjects were then operated on, and allowed 14 days in which to recover. Unoperated control subjects were rested for an equivalent period. Post-operatively, all subjects were run for 10 sessions on a geometric progressive ratio schedule. The initial five reinforcements required 1, 4, 6, 10, 12, responses. Thereafter each response-requirement was approximately 1.25 times the preceding requirement. Each session terminated when the 'break-point' criterion (Hodos, 1961) of 15 min. with no responding was achieved. Following each session the total number of responses, the elapsed time and the 'breakpoint' were recorded.
RESULTS There was considerablle variability both by a given subject from day to day, and between subjects on a given day, in all measures of progressive ratio performance (see Table 1) . When analysed by Group X Days analyses of variance (Winer, 1962) only two of the dependent variables showed significant mean differences. There was a significant reduction in the number of responses per session over days for all groups ( p < 0.05) but no significant differences between groups. However, the Groups X Days interaction was significant ( p < 0.01). This is difficult to interpret but may be attributed to the trend shown by the ventral lesion group
HIPPOCAMPAL LESIONS AND PROGRESSIVE RATIO SCHEDULE
1083
The traditional 'break-point' measure of progressive ratio performance did not differ significantly over days or groups. The over-all mean 'break-point' was 62 (SD = 50.9).
DISCUSSION Perseveration on a progressive ratio schedule would be most clearly shown by either an increase in the 'break-point' or by an increase in elapsed session time. In the present study, neither dorsal nor ventral hippocampal lesions led to increased perseveration measured by either of the relevanc dependent variables. The significant differences in average rate observed cannot be directly interpreted as evidence for perseveration. Examination of the topography of responding, shown in the cumulative records of this and other studies (see Stewart, Blampied, & Hughes, 1974, for examples) shows two fairly distinct patterns of responding: a high initial running rate, sometimes with pauses of various durations, followed by an abrupt transition to the terminal pause ('break-point') or a slow, steady rate with a much less abrupt transition. The control and neocortical lesion groups show a mixture of these two patterns, some subjects exhibit one pattern, some the o t h a . The higher average rate exhibited by the ventral lesion group is due to there being a majority of subjects in this group with the first kind of response topography, while the lower race in the dorsal lesion groups is due to a preponderance of subjects with the second type of pattern. Whether this difference is lesion-related or reflects a sampling artifact it is impossible to say. The reduction in responses over sessions may be interpreted as an adaptation to the schedule, with response suppression occurring in response to the aversive properties of the progressive ratio schedule (Dardano, 1973; Findley, 1958; Hurwitz & Harzem, 1968 ). Over-all, the conservative conclusion is that hippocampal lesions did not produce significant changes in geometric progressive ratio performance. This is in agreement with the findings of Carey (1969), but not those of Ehrlich ( 1963) or Schmaltz, et al. ( 1973). These differences may reflect not only differences in the schedules employed, but also in the nature of the pre- and postoperative experience which preceded testing on the particular schedules, since prior experience and its relationship to the operation have been found to be important variables determining the performance of hippocampally lesioned animals on a variety of tasks (Fried, 1972, 1973). Failure to observe perseveration following hippocampal lesions has quite serious implications for several theories of hippocampal functioning (Douglas, 1967; Kimble, 1968), since it is from the observation of perseveration that the inference of loss of inhibitory function is made. The present results support those who view the hippocampus as being involved in the regulation or adaptation of behavior to sudden changes in the animal's environrnenc and/or reinforcement contingencies.
1084
W. J. STEWART
&
N. M. BLAMPIED
REFERENCES CAREY,R. J. Motivational and reinforcement scheduling factors in the effect of hippocampal injury on operant behavior. Physiology and Behavior, 1969, 4, 959-961. DARDANO,J. F. Self-imposed time-outs under increasing response requirements. Journal o f the Experimental Analysis of Behavior, 1973, 19, 269-287. DOUGLAS,R. J. The hippocampus and behavior. Psychological Bulletin, 1967, 67, 416442. EHRLICH,A. Effects of tegmental lesions on motivated behavior in rats. Journal o f Compurative and Physiological Psychology, 1963, 56, 390-396. FINDLEY,J. D. Preference and switching under concurrent schedules. Journal of the Experimenral Analysis of Behavior, 1958, 1, 123-144. FRIED,P. A. The effect of differential hippocampal lesions and pre- and ost operative training on extinction Cundiun Journul o f Psychology. 1972, 26. FRIED,P. A. The interaction of inter-trial intervals, timing of surgery, and differential hippocampal lesions. British Journal of Psychology, 1973, 64, 115-126. H o ~ o s ,W. Progressive ratio as a measure of reward strength. Science, 1961, 134, 943944. HURWI'IZ,H. M. B., & HARZEM, P. Progressive ratio performance with reset option. Psychologicul Record, 1968, 18, 553-558. K ~ B L ED., P. Hippocampus and internal inhibition. Psychological Bulletin, 1968, 70, 285-295. NADEL,L. Dorsal and ventral hippocampal lesions and behaviour. Physiology and Behavior, 1968, 3, 891-900. PELLEGRINO, L. J., & CUSHMAN,A. J. A stereotaxic atlas o f the rut bruin. New York: Appleton-Century-Crofts, 1967. RABE,A., & HADDAD,R. K. Effect of selective hippocampal lesions in the rat on acquisition, performance and extinction of bar-pressing on a fixed ratio schedule. Experimental Bruin Research, 1968, 5 , 259-266. S W L n , L. W., WOLF, B. P., & TREJO,W. R. FR, DRL and discrimination learning in rats following aspiration lesions and penicillin injection into hippocampus. Physiology und Behavior, 1973, 11, 17-22. STEWART,W. J., BLAMPIED, N. M., & HUGHES,R. N. The effects of sco olamine on performance on a geometric progressive ratio schedule. ~sychoplurmacolo~ia (Bed.), 1974, 38, 55-66. WINER, B. J. Stafisfical principles in experimenful design. New York: McGraw-Hill, 1962.
18-70
Accepted September 5 , 1975.
9. STEWART
AND N. M. BLAMPIEDa
Canterbury, Christchurch, N. Z.
Univer~ityof
Summary.-Previous research has frequently reported that hippocampally lesioned rats perseverate. On a geometric progressive ratio schedule, i n which reinforcement contingencies became gradually more adverse, rats with dorsal or ventral hippocampal lesions did not perseverate more than cortically lesioned or unoperated controls (ns = 7, 8 ) . There was a significant reduction in the number of responses pea session over the 10 experimental days, for all groups. Animals with lesions of the hippocampus are frequently said to perseverare (Douglas, 1 9 6 7 ) , i.e., they continue to exhibit non-adaptive patterns of behaviour which non-lesioned animals either d o not emit at all or rapidly cease to emit. And, lesioned animals continue to respond longer in t h e face of adverse experimental conditions. O n simple fixed ratio schedules, hippocampally lesioned subjects respond more rapidly than control subjects (Rabe & Haddad, 1968). W h e n exposed to a succession of increasing fixed ratio schedules (successive ratio) hippocampally lesioned subjects have also been found to respond at higher rates than controls o n some of the ratio schedules (Ehrlich, 1963; Schmaltz, Wolf, & Trejo, 1973). Carey ( 1969), however, found no difference between hippocampally lesioned and control subjects o n a successive ratio schedule. T o date, the effect of hippocampal lesions on performance on a true progressive ratio schedule, in which the number of responses required for reinforcement increases systematically following each reinforcement, has not been reported, although such a schedule would seem to provide an appropriate test of the perseveration hypothesis since it confronts the animal with increasingly adverse conditions of reinforcement, but without abrupt changes in reinforcemenc density or character (Findley, 1958). Since arithmetic progressions approximate to fixed ratios at high values, a geometric progression was used in the present study. Because of evidence that dorsal and ventral hippocampal lesions may have different behavioral effects (Nadel, 1968) lesions were distributed within the hippocampus.
METHOD Subjectr Twenty-eight rats (Otago-N. Z. Black-White strain), 120 to 200 days old, 'Now at La Trobe University, Victoria, Australia. 'Address reprint requests to N. M. Blampied. Research supported by Grants C70/20, 70/44, 72/24, and 73/2/34 to N. M. B. Research reported was performed in partial fulfillment of the requirement of the M.Sc. degree by W.J.S.
1080
W. J. STEWART & N. M. BLAMPIED
were used. They were housed individually and kept at 80% of their free-feeding weight for the duration of the experiment except for a few days pre- and postoperatively. Twenty-one animals were lesioned; 6 in the neocortex (males), seven in the ventral hippocampus ( 1 female, 6 males) and 8 in the dorsal hippocampus ( 7 males, 1 female). The other 7 racs ( 5 females, 2 males) served as unoperated controls.
Apparatus A standard Grason-Stadler rat Skinner box, enclosed in a sound-attenuating chest with an exhaust fan which masked external noise, was used. It was illuminated by a fluorescent strip mounted 12 cm above the Skinner box. The Skinner box contained a single bar mounted to the right of a central dipper hole through which liquid food (milk enriched with 'Complan') could be delivered 0.05 ml at a time. Programming of reinforcements was carried out by standard electro-mechanical devices. Reinforcements were scheduled by a Gerbrands Ratio Programmer. Following premedication with acetyl-promazine and atropine sulphate injected intramuscularly, animals were anesthetized with chloral hydrate (350 mg/kg). Bilateral electrolytic lesions were produced srereotaxically by passing 3-mA anodal current for 10 sec. through a stainless steel, acrylic-insulated electrode. The cathode was moistened with saline and attached to the tail. Coordinates were taken from the Pellegrino and Cushman (1967) atlas and were as follows: anterior-posterior: -4.0 mm; lateral: 3.0 mm (all groups); depth: 1.5 mm neocortical; 3.0 mm dorsal hippocampus; 7.5 mm ventral hippocampus. The electrode was angled at 20' from the vertical for the dorsal and ventral hippocampal lesions.
Histology The lesioned rats were sacrificed with an overdose of sodium pentobarbital and perfused with saline and formalin. The extracted brains were left in formalin solution for 15 days then sectioned at 100-150r. Sections were mounted, stained with thioin and examined under a microscope. Several subjects had to be reassigned to different groups. Three racs in the dorsal hippocampal group suffered damage to the thalamus and were grouped separately in subsequent analysis. One ventral hippocampal subject suffered thalamic damage - and its results were discarded. The maximum and minimum damage to the various regions are shown in Fig. 1. The most extensive neocortical lesions extended slightly into the dorsal hippocampus; while the largest ventral hippocampal lesions extended into the entorhinal cortex.
HIPPOCAMPAL LESIONS AND PROGRESSIVE RATIO SCHEDULE
1081
FIG. 1 Reconstructions of the largest and smallest lesions found in the animals 1esioned in the neo-cortex, dorsal hippocampus, and ventral hippocampus (from Pellegrino & Cushman, 1967) Proced~~e Following deprivation, and adaptation to the Skinner box subjects were trained to bar-press by successive approximation. They were then given one session of 80 continuous reinforcements. Lesion-group subjects were then operated on, and allowed 14 days in which to recover. Unoperated control subjects were rested for an equivalent period. Post-operatively, all subjects were run for 10 sessions on a geometric progressive ratio schedule. The initial five reinforcements required 1, 4, 6, 10, 12, responses. Thereafter each response-requirement was approximately 1.25 times the preceding requirement. Each session terminated when the 'break-point' criterion (Hodos, 1961) of 15 min. with no responding was achieved. Following each session the total number of responses, the elapsed time and the 'breakpoint' were recorded.
RESULTS There was considerablle variability both by a given subject from day to day, and between subjects on a given day, in all measures of progressive ratio performance (see Table 1) . When analysed by Group X Days analyses of variance (Winer, 1962) only two of the dependent variables showed significant mean differences. There was a significant reduction in the number of responses per session over days for all groups ( p < 0.05) but no significant differences between groups. However, the Groups X Days interaction was significant ( p < 0.01). This is difficult to interpret but may be attributed to the trend shown by the ventral lesion group
HIPPOCAMPAL LESIONS AND PROGRESSIVE RATIO SCHEDULE
1083
The traditional 'break-point' measure of progressive ratio performance did not differ significantly over days or groups. The over-all mean 'break-point' was 62 (SD = 50.9).
DISCUSSION Perseveration on a progressive ratio schedule would be most clearly shown by either an increase in the 'break-point' or by an increase in elapsed session time. In the present study, neither dorsal nor ventral hippocampal lesions led to increased perseveration measured by either of the relevanc dependent variables. The significant differences in average rate observed cannot be directly interpreted as evidence for perseveration. Examination of the topography of responding, shown in the cumulative records of this and other studies (see Stewart, Blampied, & Hughes, 1974, for examples) shows two fairly distinct patterns of responding: a high initial running rate, sometimes with pauses of various durations, followed by an abrupt transition to the terminal pause ('break-point') or a slow, steady rate with a much less abrupt transition. The control and neocortical lesion groups show a mixture of these two patterns, some subjects exhibit one pattern, some the o t h a . The higher average rate exhibited by the ventral lesion group is due to there being a majority of subjects in this group with the first kind of response topography, while the lower race in the dorsal lesion groups is due to a preponderance of subjects with the second type of pattern. Whether this difference is lesion-related or reflects a sampling artifact it is impossible to say. The reduction in responses over sessions may be interpreted as an adaptation to the schedule, with response suppression occurring in response to the aversive properties of the progressive ratio schedule (Dardano, 1973; Findley, 1958; Hurwitz & Harzem, 1968 ). Over-all, the conservative conclusion is that hippocampal lesions did not produce significant changes in geometric progressive ratio performance. This is in agreement with the findings of Carey (1969), but not those of Ehrlich ( 1963) or Schmaltz, et al. ( 1973). These differences may reflect not only differences in the schedules employed, but also in the nature of the pre- and postoperative experience which preceded testing on the particular schedules, since prior experience and its relationship to the operation have been found to be important variables determining the performance of hippocampally lesioned animals on a variety of tasks (Fried, 1972, 1973). Failure to observe perseveration following hippocampal lesions has quite serious implications for several theories of hippocampal functioning (Douglas, 1967; Kimble, 1968), since it is from the observation of perseveration that the inference of loss of inhibitory function is made. The present results support those who view the hippocampus as being involved in the regulation or adaptation of behavior to sudden changes in the animal's environrnenc and/or reinforcement contingencies.
1084
W. J. STEWART
&
N. M. BLAMPIED
REFERENCES CAREY,R. J. Motivational and reinforcement scheduling factors in the effect of hippocampal injury on operant behavior. Physiology and Behavior, 1969, 4, 959-961. DARDANO,J. F. Self-imposed time-outs under increasing response requirements. Journal o f the Experimental Analysis of Behavior, 1973, 19, 269-287. DOUGLAS,R. J. The hippocampus and behavior. Psychological Bulletin, 1967, 67, 416442. EHRLICH,A. Effects of tegmental lesions on motivated behavior in rats. Journal o f Compurative and Physiological Psychology, 1963, 56, 390-396. FINDLEY,J. D. Preference and switching under concurrent schedules. Journal of the Experimenral Analysis of Behavior, 1958, 1, 123-144. FRIED,P. A. The effect of differential hippocampal lesions and pre- and ost operative training on extinction Cundiun Journul o f Psychology. 1972, 26. FRIED,P. A. The interaction of inter-trial intervals, timing of surgery, and differential hippocampal lesions. British Journal of Psychology, 1973, 64, 115-126. H o ~ o s ,W. Progressive ratio as a measure of reward strength. Science, 1961, 134, 943944. HURWI'IZ,H. M. B., & HARZEM, P. Progressive ratio performance with reset option. Psychologicul Record, 1968, 18, 553-558. K ~ B L ED., P. Hippocampus and internal inhibition. Psychological Bulletin, 1968, 70, 285-295. NADEL,L. Dorsal and ventral hippocampal lesions and behaviour. Physiology and Behavior, 1968, 3, 891-900. PELLEGRINO, L. J., & CUSHMAN,A. J. A stereotaxic atlas o f the rut bruin. New York: Appleton-Century-Crofts, 1967. RABE,A., & HADDAD,R. K. Effect of selective hippocampal lesions in the rat on acquisition, performance and extinction of bar-pressing on a fixed ratio schedule. Experimental Bruin Research, 1968, 5 , 259-266. S W L n , L. W., WOLF, B. P., & TREJO,W. R. FR, DRL and discrimination learning in rats following aspiration lesions and penicillin injection into hippocampus. Physiology und Behavior, 1973, 11, 17-22. STEWART,W. J., BLAMPIED, N. M., & HUGHES,R. N. The effects of sco olamine on performance on a geometric progressive ratio schedule. ~sychoplurmacolo~ia (Bed.), 1974, 38, 55-66. WINER, B. J. Stafisfical principles in experimenful design. New York: McGraw-Hill, 1962.
18-70
Accepted September 5 , 1975.
