Effects of additional cues on passive avoidance learning and extinction in rats with hippocampal lesions

Following the acquisition of a water-rewarded approach response in a straight runway, the effects of introducing shock in the goal box (passive avoidance - PA) or withdrawing reinforcement (extinction) were compared in hippocampal, cortical, and operated control groups of rats. Under standard test conditions, hippocampal groups were impaired in PA learning and showed strong resistance to extinction, relative to the control groups. When additional cues were provided such that external stimuli associated with goal box events could be easily detected early in the runway, performance differences between the hippocampal and control groups were eliminated in the PA test and significantly reduced in extinction. The results emphasize the inefficient processing by hippocampally-damaged animals of stimulus cues following a shift in experimental contingencies.     

Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction

The effects of pimozide were examined in a runway paradigm using food reward. Rats received one of three doses of pimozide, vehicle or Ringer's prior to testing. Two additional groups received pimozide or vehicle after the test trial in the home cage. An extinction group received no food in the goal box on test days. Several components of running behavior were assessed as was food consumed in the goal box. Effects of pimozide on general locomotor activity were assessed in the open-field following the runway phase. Results of the runway indicated that pimozide-treated rats differed from the extinction group in latencies to leave the start box and enter the goal box. Pimozide-treated rats consumed less saccharin-flavored food than controls. The post-treatment pimozide group showed a reduction in saccharin-food intake suggesting a conditioned taste aversion. Thus, the reduction observed in the pretreated pimozide group may be due to some unconditioned aversion induced by the drug. Open-field revealed that pimozide resulted in lower activity than controls. This study indicates that the effects of pimozide on food reinforcement are not similar to the effects seen in extinction. These data are consistent with the hypothesis that the effects of pimozide, in this paradigm, constitute an interference with motor responses as opposed to an attenuation of reward properties of the stimuli.     

Lesions in the amygdala and the frustration effect

Responding in a double runway following the omission of reinforcement in the first goal box was investigated in rats with lesions in the amygdala. Analysis of runway speeds indicated that bilateral lesions in the amygdala prevented the occurrence of the frustration effect in the second alley and produced decreased vigor of performance in the first alley. Results were discussed in terms of frustration and changes in motivation.     

The effect of cytotoxic lesions of the hippocampus on recognition memory in the rat: effects of stimulus size

Rats with excitotoxic hippocampal lesions were trained on delayed nonmatching-to-sample (DNMS) with small goal boxes, containing complex objects, presented on a pseudo trial-unique schedule. A series of experiments then tested performance on repeated presentation of either the small object or large empty goal boxes. All rats acquired the nonmatching rule, but hippocampal-lesioned rats performed less well than controls on choice accuracy for the final 2 blocks of acquisition. In the study's main phase, the lesions impaired choice accuracy when the large empty boxes were used as stimuli. This deficit was ameliorated when the rats were tested with the small object boxes, although the performance of the hippocampal-lesioned rats was still below that of controls. These results extend previous reports of box size-dependent effects of hippocampal aspiration lesions on DNMS and suggest that selective damage to the hippocampus, not neuronal loss in adjacent structures or fiber tracts, is critical for the effect.     

Locus coeruleus lesions and learning in the rat.

The performance of rats with bilateral lesions of the nucleus locus coeruleus (LC) was compared with that of sham-lesioned rats using 3 avoidance and 2 appetitive learning paradigms. LC lesions which significantly reduced cortical norepinephrine produced no deficits in learning one-way active or passive shock avoidance responses, nor in acquisition or extinction of a conditioned taste aversion, nor in acquisition of a bar press response for food reinforcement, but did produce impairments in running for food in an L-shaped runway. The runway deficit could not be related to motor difficulties or differences in activity between the two groups. Although locus coeruleus lesions interfere with performance in a runway task they do not produce a general impairment in learning.     

Influence of amygdaloid lesions on self-punitive behavior in rats

Self-punitive or masochistic behavior describes a phenomenon in which, during the extinction of escape behavior, rats will leave a start box and cross an electrified shock grid to enter a goal. Rats need only remain in the start box to avoid shock, yet they persist in running into shock. In the present study this self-punitive behavior was eliminated by bilateral lesions of the caudal amygdala. Analyses of the running speeds indicate that the lesions left the pain inducing properties of shock intact, while decrementing the fear produced by shock. Evidence was taken as support for the Mowrer — Brown explanation of self-punitive behavior as a product of conditioned fear.     

Brain structures important for solving a sawdust-digging problem in the rat

Young rats subjected to bilateral lesions to one of 37 different brain sites were initially trained to traverse a narrow runway to reach a goal box containing water. The test involved blocking a portion of the runway with sawdust and determining whether the animals would burrow through the sawdust to gain access to the goal box. Lesions to 30 brain sites produced deficient performance on the sawdust-digging problem. This study, combined with earlier investigation of 11 additional brain sites, shows that 41 of 48 total brain sites are involved in this task. These findings suggest that underlying brain mechanisms include a nonspecific mechanism and several specific mechanisms, such as visuospatial-attentional, visual discrimination, vestibular-proprioceptive-kinesthetic discrimination, response flexibility, but much less place learning mechanisms.     

Motivational effects of nicotine as measured by the runway method using priming stimulation of intracranial self-stimulation behavior

It is well known that priming stimulation promotes the motivational effects of intracranial self-stimulation(ICSS) behavior. An experimental methodology using the runway method could separately study the reward and motivational effects of ICSS behavior. In the present study, we examined the motivational effect of nicotine as measured by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus, and rats were trained to get a reward stimulation (50-200 microA, 0.2 ms, 60 Hz) of MFB when the goal lever was pressed. After the rats were trained to press the lever, a priming stimulation of the MFB was performed. After receiving the priming stimulation, rats were placed at the start box of the runway apparatus, and the running time duration until the goal lever was pressed was measured. Subcutaneous injection of nicotine at a dose of 0.2mg/kg produced an increase in running speed to obtain the reward stimulation, and priming stimulation facilitated the motivational effect to obtain the electrical brain stimulation reward in the rats. These results suggest that nicotine significantly enhanced the motivational effect on ICSS behavior as determined using the runway method. The runway method using priming stimulation of ICSS behavior may become the new experimental methodology with which to measure the motivational effect of some drugs.     

Intact selective attention in rats with lesions of the dorsal noradrenergic bundle

Mason's hypothesis (1980) was tested that lesions of the dorsal noradrenergic bundle (DNB), which induce depletion of forebrain noradrenaline, alter performance of discrimination tasks because they retard habituation to naturally attractive, but instrumentally irrelevant, stimuli. In Experiment 1, groups of rats with either vehicle or 6-hydroxydopamine injections into the DNB were assigned to five different discrimination tasks in a cross-maze with black and white goal arms. The tasks were acquisition and reversal of position, visual, or turn discrimination, and acquisition of visual or turn discrimination followed by a shift to the alternative discrimination. In spite of evidence that the rats preferred to attend more to the visual stimuli of the goal arms than to directions of turns, lesions of the DNB did not impair acquisition and reversal of turn discrimination with visual stimuli irrelevant, and did not facilitate performance of turn-to-visual shift. In fact, the lesions did not alter performance of any tasks. In Experiment 2, control and noradrenaline-depleted rats were trained in a task of light-dark discrimination followed by shift to position discrimination in a Y-maze. At the onset of training, the rats of both groups reliably avoided the bright goal arm and responded to the dark goal arm, thus demonstrating predominant attention for the relevant brightness stimuli rather than the irrelevant position stimuli. The DNB lesions impaired acquisition of brightness discrimination only when the positive stimulus was the illuminated goal arm, and they did not alter shift performance. These results do not support the hypothesis at test. On the other hand, they indicate that DNB lesions in the rat can impair habituation of light avoidance.     

Lesions in the ventromedial hypothalamus and response to frustrative nonreward

Bilateral lesions in the ventromedial hypothalamus of rats increased the frustration effect in a double runway. Following the omission of reward in the first goal box, rats with lesions ran faster than controls in the second alley. Results were discussed in terms of changes in motivation and reactivity to aversive events.     

Cue-induced recall of a passive avoidance response by rats with hippocampal lesions

Two experiments are reported in which a stimulus reminder technique was used in an attempt to compensate for the disruptive effects of hippocampal lesions on passive avoidance (PA) conditioning. Groups of hippocampal, cortical and operated control rats were trained to run down an alley for water reward. When the approach response had stabilized, shock was introduced in the goal-box, resulting in increased running times in the control groups and the characteristic PA impairment in the hippocampal group. A recall test was administered 24 hr later but 2 hr before the test, animals were reminded of the previous treatment by being exposed to: (1) shock and related stimuli, (2) related stimuli only, or (3) neutral stimuli. The PA performance of the hippocampus groups in the recall test improved to the level of controls following conditions 1 or 2; there was no effect of condition on Treatment 3. Performance of control groups was virtually unaffected by any of the reminder conditions. The similarities were noted between these results and those of partial cueing studies involving human amnesics with known or suspected damage to the hippocampal system.     

Preoperative differential housing and dorsal hippocampal lesions in rats

Rats housed in impoverished environments often show greater behavioral deficits after receiving brain lesions than to rats housed in standard or enriched environments. However, the resemblance between the effects of social isolation and those of hippocampal lesions in rats prompted the suggestion that rats socially isolated at weaning rather than grouped counterparts may show less behavioral change after sustaining dorsal hippocampal lesions when adult. In socially reared rats, hippocampal lesions produced increased ambulation and object contact in an open field, reduced passive avoidance in a runway task, and produced faster acquisition of active avoidance in a shuttle box, but there were no such differences in isolation-reared rats. Ambulation and object contact in isolates were intermediate to those of rats with lesions and intact group-housed rats, and the behavior of isolates during passive and active avoidance training was generally similar to that of grouped rats with lesions. The introduction of a distractor during approach training in an alley reduced running speeds more in rats with lesions than in controls. The several significant interactions between housing state and lesion state suggest that neural pathways associated with the hippocampal formation may mediate some behavioral effects of differential housing.     

Parietal cortex lesions do not impair retention performance of rats in a 14-unit T-maze unless hippocampal damage is present

Young male F-344 rats, pretrained in a straight runway to avoid shock, were then trained in a shock-motivated 14-unit T-maze. One day after maze acquisition, extensive parietal cortex lesions (PC) or sham operations (CON) were performed to assess possible involvement of parietal cortex in the age-related impairment previously observed in this task. Twelve days after surgery, a first 10-trial retention session in the 14-unit T-maze was conducted. One day later the vibrissae of half the rats in each group were clipped to examine involvement of the damaged barrel cortex field in maze performance of rats with PC lesions. The following day a second 10-trial retention session occurred. Finally, retention of the straight runway avoidance response was tested. Histological verification revealed a group with consistent parietal damage but also a subgroup with relatively small lesions to dorsal or lateral hippocampus in addition to parietal damage (PC + HIP). Behavioral results revealed virtually perfect maze retention for CON and PC rats. In contrast, PC + HIP rats were severely impaired in maze retention performance. Retention of the straight runway avoidance response was perfect in CON and PC rats but was impaired in PC + HIP rats. Vibrissae clipping did not affect error performance in the maze but led to a transitory increase in runtime. Overall, the results indicate that parietal lobe damage shortly after acquisition does not impair retention performance of young rats in the 14-unit T-maze, unless hippocampal damage is also evident. Thus, parietal lobe dysfunction alone would not appear to be involved in the age-related retention impairment previously observed in this task.     

Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is characterized by stress-induced symptoms including exaggerated fear memories, hypervigilance and hyperarousal. However, we are unaware of an animal model that investigates these hallmarks of PTSD especially in relation to fear extinction and habituation. Therefore, to develop a valid animal model of PTSD, we exposed rats to different intensities of footshock stress to determine their effects on either auditory predator odor fear extinction or habituation of fear sensitization. In Experiment 1, rats were exposed to acute footshock stress (no shock control, 0.4 mA, or 0.8 mA) immediately prior to auditory fear conditioning training involving the pairing of auditory clicks with a cloth containing cat odor. When presented to the conditioned auditory clicks in the next 5 days of extinction testing conducted in a runway apparatus with a hide box, rats in the two shock groups engaged in higher levels of freezing and head out vigilance-like behavior from the hide box than the no shock control group. This increase in fear behavior during extinction testing was likely due to auditory activation of the conditioned fear state because Experiment 2 demonstrated that conditioned fear behavior was not broadly increased in the absence of the conditioned auditory stimulus. Experiment 3 was then conducted to determine whether acute exposure to stress induces a habituation resistant sensitized fear state. We found that rats exposed to 0.8 mA footshock stress and subsequently tested for 5 days in the runway hide box apparatus with presentations of nonassociative auditory clicks exhibited high initial levels of freezing, followed by head out behavior and culminating in the occurrence of locomotor hyperactivity. In addition, Experiment 4 indicated that without delivery of nonassociative auditory clicks, 0.8 mA footshock stressed rats did not exhibit robust increases in sensitized freezing and locomotor hyperactivity, albeit head out vigilance-like behavior continued to be observed. In summary, our animal model provides novel information on the effects of different intensities of footshock stress, auditory-predator odor fear conditioning, and their interactions on facilitating either extinction-resistant or habituation-resistant fear-related behavior. These results lay the foundation for exciting new investigations of the hallmarks of PTSD that include the stress-induced formation and persistence of traumatic memories and sensitized fear.     

Fornical lesions and aversievely-motivated behavior in the rat

Rats with fornical, septal, and combined septal and fornical damage were compared with control rats on the acquisition of a one-way avoidance response, the forced extinction of that response, the acquisition of a shock-motivated position habit and the reversal of that habit. The rats with septal lesions were deficient in one-way avoidance acquisition, position-habit acquisition, and position-habit reversal. The rats with fornical or combined septal and fornical lesions were deficient in reversing the position habit. Their performance on the other tasks was not statistically different from that of the septal or control animals.     

Red ginseng ameliorated place navigation deficits in young rats with hippocampal lesions and aged rats

Effects of hippocampal lesions and aging on spatial learning and memory and ameliorating effects of red ginseng on learning deficits were investigated in the following two experiments: performance of young rats with selective hippocampal lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham-operated or intact young rats. Each rat in these two behavioral experiments was tested with the three types of spatial-learning tasks (distance movement task, DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a circular open field using intracranial self-stimulation as reward. The results in the DMT and RRPST tasks indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng were not significantly different from that of sham-operated young rats in Experiment 1. However, young rats with hippocampal lesions displayed significant deficits in the PLT task. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions on the PLT task. Similarly, red ginseng improved performance of aged rats on the PLT task in Experiment 2. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation.     

Retrograde amnesia for fear-potentiated startle in rats after complete,but not partial,hippocampal damage

We assessed the involvement of the hippocampus in recall of learned fear of a discrete visual stimulus using a fear-potentiated startle (FPS) procedure. Recall was measured by an increase in acoustic startle in the presence of a light that was paired with footshock. In Experiment 1, rats either received sham, dorsal, ventral, or complete (dorsal and ventral) NMDA-induced damage of the hippocampus following FPS acquisition. During the post-surgery retention test, only the rats with complete hippocampal damage showed a significant FPS deficit. In Experiment 2, we examined whether recent and remote memory for FPS would be differentially affected by complete hippocampal damage. Rats received sham or complete hippocampal damage 1- or 4-wk after FPS acquisition. During the retention test, sham rats exhibited significant FPS, whereas rats with hippocampal damage showed a large FPS deficit that was equivalent for recent and remote memories. In Experiment 3, we found that rats with complete hippocampal damage induced before conditioning showed levels of FPS that did not significantly differ from sham rats. Combined, these findings suggest that extensive damage to the hippocampus causes retrograde amnesia for a memory involving a light–shock association that is not temporally graded. The same damage does not cause anterograde amnesia in the same memory task. Partial damage of the hippocampus, whether of the dorsal or ventral region, was insufficient to cause retrograde amnesia. Thus, the hippocampus normally has a critical and long-lasting role enabling recall of fear conditioning to a discrete visual stimulus. In the absence of the hippocampus other memory systems support new learning.     

Failure to transfer a digging response to a detour problem in young rats with lesions to the "general learning system"

Recent lesion studies on young rats suggest that the components of the rodent's general learning system (GLS; a group of brain structures essential for normal acquisition of a wide range of laboratory tasks, include the regions of the caudatoputamen, globus pallidus, ventrolateral thalamus, substantia nigra, ventral tegmental area, superior colliculus, median raphe, and pontine reticular formation). The current study provides evidence that young GLS-lesioned rats, like mentally retarded humans, may be suffering from a disturbance in some superordinate ability (executive functioning) that controls the use of learning strategies in general and the transfer of learning in particular. Specifically, thirsty rats were initially trained to traverse a narrow runway to reach a goal box containing water. When a portion of the runway was blocked with sawdust, all of the sham-operated control rats succeeded in burrowing through the sawdust to gain access to the goal box, whereas most of our GLS-lesioned rats failed to do so even though they "knew how" to dig. Neocortically damaged rats showed a similar though significantly smaller deficit. Although other interpretations are possible, these data give tentative support to the view that this impairment in transfer reflects a defect in executive processing.     

Blocking can occur without losses in attention in rats with selective removal of hippocampal cholinergic input

Prior studies showed that 192 IgG-saporin lesions of cholinergic input to the hippocampus disrupted reductions in processing of uninformative stimuli. In 2 experiments in this study, the performance of rats with these lesions was examined in blocking procedures. In both lesioned and normal rats, previous pairing of one conditioned stimulus (CS) with food blocked conditioning of a 2nd CS when a compound of both CSs was paired with food. However, in subsequent savings tests, lesioned rats showed faster learning than did normal rats when the blocked CS was established as a signal for either reinforcement or nonreinforcement. Thus, the reduced attention to the blocked CS found in normal but not lesioned rats was not essential for the occurrence of blocking. Although rats with selective removal of hippocampal cholinergic input may be unable to reduce attention to redundant stimuli, other mechanisms of stimulus selection remain available to them.     

Effects of interrun interval shift in the reward serial learning of the rat on the straight runway

Using runway training procedure, three experiments examined effects of interrun interval (IRI) shift on serial pattern learning in rats. Series consisted of varying number of 0.045 g food pellets given in a goal box of a runway. Groups of rats were trained with 24-10-1-0 or 24-16-10-6-3-1-0 series (Experiment 1), 14-7-3-1-0 series (Experiment 2), and 18-12-6-3-1-0 or 18-7-7-7-1-0 series (Experiment 3), under either short (15-20 s) or long (5-15 min) IRI. In test phases, IRI was shifted from short to long or vice versa. Anticipation of 0 pellet was not disrupted by shortening of IRI, whereas lengthening of IRI eliminated the 0 pellet anticipation of the five- to seven-item monotonic series but did not eliminate that for the four-item series and the nonmonotonic series. These results suggest that rats learn a series with different strategies depending on IRI, pattern length, or structural complexity of a series.