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Previous studies have shown that several aryl hydrocarbon receptor (AHR) agonists, including β-naphthoflavone (BNF), elicit avoidance of novel food items in rodents, with this behavioral response displaying a similar doseresponse to hepatic induction of CYP1A1. The avoidance has been found to bear substantial similarity to conditioned taste avoidance/aversion (CTA). The present study set out to confirm the indispensability of AHR in the avoidance response, to verify whether vagal afferent fibers are involved in it, and to see if AHR signaling might interfere with the effect of the classic trigger of CTA, LiCl. To this end, globally AHR deficient (AHRKO) or vagotomized wildtype rats were treated by gavage with 60 mg/kg BNF or ip with 0.15M LiCl (4 ml/kg), and presented with chocolate which was either novel or familiar to them. Both the avoidance response and Cyp1a1 induction were missing in AHRKO rats. In contrast, Ahr+/− rats exhibited them in full, save for a single outlier. Total subdiaphragmatic vagotomy failed to interfere with the avoidance of novel or familiar chocolate or induction of Cyp1a1. After LiCl administration, male AHRKO rats showed a significantly mitigated suppression of chocolate consumption compared with wildtype animals (~60% vs. ~10% of control chocolate intake, respectively). A similar tendency was seen in females, but they were less responsive to LiCl. These findings corroborate AHR as a prerequisite of the BNF-induced novel food avoidance, prove vagal afferents unlikely mediators of this response, and imply an unforeseen involvement of AHR signaling in the thoroughly-characterized CTA instigated by LiCl.

This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms.

Analyses of the behavioral reactions of rodents to predators have greatly contributed to the understanding of defense-related human psychopathologies such as anxiety and panic.We here investigated the behavioral consequences of exposing male Wistar rats to a live cat using the elevated T-maze test of anxiety. This test allows the measurement of two defensive responses: inhibitory avoidance and escape, which in terms of pathology have been associated with generalized anxiety and panic disorders, respectively. For comparative reasons, the effects of exposure to the cat were also assessed in the elevated plus-maze. The results showed that a 5-min exposure to the cat selectively facilitated inhibitory avoidance acquisition, an anxiogenic effect, without affecting escape expression in the elevated T-maze. This was seen immediately but not 30 min after contact with the predator. This short-lived anxiogenic effect was also detected in the elevated plus-maze. Previous administration of the benzodiazepine anxiolytic diazepam (2 mg/kg) decreased the immediate avoidance response to the predator and the neophobic reaction to a dummy cat used as a control stimulus. The drug also impaired inhibitory avoidance acquisition in the elevated T-maze, indicating an anxiolytic effect, without affecting escape performance. The results indicate that the state of anxiety evoked during contact with the predator generalizes to both elevated plus- and T-mazes, impacting on defensive responses associated with generalized anxiety disorder.

The inbred RLA (Roman Low-Avoidance) and RHA (Roman High-avoidance) rat strains have been psychogenetically selected for rapid (RHA) vs. extremely poor acquisition (RLA) of two-way active avoidance. As a consequence of this selective breeding, RLA animals exhibit a higher level of emotionality that can be observed in many anxiety models. The present study was conducted in order to analyze the performance of female RLA, RHA and Wistar rats in a behavioral test of anxiety that involves the reduction of the magnitude of an expected reward: the negative contrast effect that is obtained in one-way avoidance learning by reducing the time spent in the safe compartment. To this aim, three groups of animals (30-1/RLA, 30-1/RHA and 30-1/W) were trained to avoid an electric foot-shock administered in a "danger" compartment, by running from this compartment to a "safe" compartment. We observed an impairment of the avoidance response when time spent in the safe compartment was reduced from 30 to 1 s, when 30-1/RLA and 30-1/W groups were compared with control groups that were trained with a constant safe time (1-1/RLA and 1-1/W, respectively). We also obtained significant differences between 30-1/RLA and 30-1/RHA groups in the postshift phase. These results indicate that RLA rats respond more negatively to the frustration triggered by the reduction in time spent in the safe compartment, suggesting that animal models based on negative contrast effects can be useful tools for studying the genetic basis of anxiety.

Previously, we reported that high- and low-avoidance animals (HAA and LAA, respectively), selectively bred for different avoidance response rates in a shuttlebox avoidance test, showed additional behavioral differences in wheel cage activity and in water maze performance after weaning. In the present study, physical and behavioral development were examined in HAA and LAA during the preweaning period. As compared to HAA, LAA offspring showed lower body weight, delayed eye opening, poorer performance in pivoting and negative geotaxis, and increased open-field activity. A fostering study indicated that these differences observed in eye opening, pivoting, negative geotaxis, open-field activity, swimming speed, shuttlebox avoidance and wheel cage activity were independent of maternal care. Only the pup weight was strongly dependent on the maternal line. These results indicate that behavioral differences between HAA and LAA observed in the pre- and postweaning periods may be linked to the avoidance genotype, but the difference in pup weight may be caused by maternal care.

Excessive dietary Fe is known to be toxic, but the extent of neurobiological involvement is not clear. In the present study male weanling rats were fed diets containing Fe at 35 (control), 350, 3500, or 20000 ppm for 12 wk. An Fe-deficient group (4 ppm) was included for comparison. Rats were tested for behavioral and body weight changes at various times after initiation of diets, and liver and brain nonheme Fe were measured at term. Excess dietary Fe, primarily at 20000 ppm, significantly decreased activity, habituation, reflex startle, and conditioned avoidance response performance, and enhanced prepulse modulation of startle. Body weights were also markedly decreased. Fe-deficient animals showed similar behavioral effects but more moderate body weight changes. Liver nonheme Fe varied directly with dietary levels. Whole-brain nonheme Fe was significantly reduced in Fe-deficient animals but increased only at the 20000-ppm level. Homeostatic mechanisms appear to regulate whole-brain Fe more effectively under conditions of dietary Fe overload than under conditions of Fe deficiency. The behavioral changes associated with dietary Fe overload may represent secondary consequences of systemic toxicity.

The effects of calcitonin gene-related peptide (CGRP) on the extinction of active avoidance behaviour was examined in rats. Three doses (250 ng, 500 ng and 1 microgram) of the peptide were administered into the lateral brain ventricle (i.c.v.). CGRP delayed the extinction of an active avoidance response in a dose-dependent manner. To reveal any role of the transmitter systems in the action of exogenously administered CGRP, the animals were pretreated with different receptor blockers. CGRP induced a delay in the extinction of an active avoidance response, which could be prevented by haloperidol, propranolol, methysergide and naloxone. Phenoxybenamine, atropine and bicuculline were ineffective. The data suggest that dopaminergic, beta adrenergic, serotonergic and opiate transmission are involved in the CGRP-induced behavioral alterations.

Behavior in the elevated plus-maze and plasma corticosterone levels were investigated in Koltushi high-avoidance (KHA) and low-avoidance (KLA) rat strains subjected to inescapable shock (IS) or daily handling for 10 days. These strains have been genetically selected on the basis of divergent acquisition of a conditioned avoidance response in a two-way shuttle-box. Naive KHA rats were more anxious than KLA ones. Following exposure to IS, the time spent in open arms was increased in KHA rats but decreased in KLA rats. After handling, the time spent in open arms increased only in KHA rats and became similar in both strains. There were no differences in plasma corticosterone levels between naive animals. Exposure to either IS or handling increased the plasma corticosterone levels in KLA rats. In KHA rats, handling reduced the plasma corticosterone levels, and exposure to IS had no effect. The present results suggest that the stress-induced changes in anxiety levels depend on the coping strategy of the subject.

This study investigates ultradian rhythm in avoidance behavior of mice, which may constitute a basic rest activity cycle (BRAC). Reaction times (RTs) of an avoidance response to a visual warning stimulus that preceded an electric shock were measured by the use of a computer-controlled shuttle box. The male naive DBA mice were brought to a criterion of 98% correct responses in numerous training sessions. For each subject, all the temporal sequences of the RTs in the trials following achievement of the criterion were examined with discrete Fourier transform. Periodograms were obtained from three sessions for each of the two animals in the first experiment and from 15 subjects in the second experiment. Analysis of the periodograms reveals a stable rhythm in avoidance behavior of mice, with a period of about 14 min. The presence of these periodicities could show the existence, also in small rodents, of a BRAC rhythm.

The relationship between performance in an avoidance conditioning paradigm and the plasma glucose levels of Sprague-Dawley rats was examined in two experiments. In Experiment 1 we investigated whether glucose levels varied with the animal's relative success at acquiring the avoidance task. Results indicated that animals classified as avoiders (60% avoidance and above) had lower glucose levels than animals classified as escapers (30% avoidance and below). In Experiment 2 we looked at whether glucose levels showed within-subject changes with avoidance acquisition. Results demonstrated that glucose levels showed reductions if an animal learned the avoidance response. Subjects that did not learn the response showed no such reduction. Such results suggest that the physiological response to stress is attenuated by acquisition of successful coping behaviors that exercise control over the onset of aversive events.

VMH-lesioned female Long-Evans hooded rats held to preoperative body weight acquired a shuttle box avoidance response only as rapidly as control animals at both a moderate and high shock level when intertrial interval crossings were not punished, and at a moderate shock intensity with punished ITI crossings. Both groups displayed 90–95% asymptotic avoidance behavior under all three conditions. Obese rats with VMH lesions displayed impaired avoidance behavior under these conditions, displaying only 55–60% asymptotic avoidance behavior after 110 trials. The impaired avoidance behavior by obese rats was not due to immobility, for they emitted as many unpunished ITI crossings as control animals. Both lean and obese rats with VMH lesions avoided a significantly greater number of shocks than control animals at a high shock intensity when ITI crossings were punished, with control animals averaging only 20% avoidance responding after 110 trials. Lean VMH rats again performed better than obese rats, displaying 85% and 60% asymptotic avoidance behavior, respectively. Lean VMH rats made more punished ITI crossings than control animals at the high shock intensity, but there was no difference between the unoperated and obese VMH-lesioned animals. Previous discrepant results with shuttle box avoidance experiments are attributed to different testing conditions, although strain differences are also possible.

Lean and obese rats with ventromedial hypothalamic lesions performed reliably worse than control animals in the acquisition of a step-down passive avoidance task. However, obese rats performed significantly better than lean VMH animals, which consistently leaped off the platform on the second and succeeding trials. While there were no significant differences between groups in the acquisition of a step-through passive avoidance task, lean and obese rats with VMH lesions took reliably longer than control animals to reach criterion when an identical step-through response had previously been reinforced (punishment-extinction of a one-way conditioned avoidance response). Both lean and obese VMH-damaged rats made more punished approach responses to water than control animals following water-deprivation to 88% of body weight, but only lean VMH rats made a significantly greater number of punished approach responses to liquid food than unoperated animals following food-deprivation to 88% of body weight. The number of punished consummatory responses appeared to be influenced by baseline intake. Among the animals tested in more than one paradigm, there was a significant positive correlation between the number of punished consummatory responses and the number of shocks received during punishment-extinction of the one-way CAR, but no relationship was observed between the performances in either of these and the step-down avoidance paradigm. The impaired passive avoidance behavior by rats with VMH lesions is attributed to both an inability to inhibit a previously reinforced response and a change in response tendencies to aversive stimuli.

Animals were exposed to infrasounds during the acquisition of a conditioned avoidance response. When compared to controls they showed performance decrements both in acquisition and retention, 24 hours later. Possible modes of action are discussed.

Male MP1 albino rats were exposed to X-irradiation in utero at a single dose of 200 R on Day 17 of gestation. This experiment was aimed to determine just how irradiated rats could differ from controls in a shuttlebox avoidance response. Irradiated rats had a significantly higher anticipatory response to CS which predicts shock, and also made a significantly higher incidence of consecutive anticipatory responses during the CS-US interval. Thus, facilitated avoidance behavior in irradiated rats is probably a consequence of a strong tendency to running induced by shock in shuttlebox. Since cell destruction caused by irradiation was evident in the primordial hippocampus, a smaller hippocampus developed. The dendrites of pyramidal neurons in Ammon's horn were abnormally oriented. Behavioral changes in shuttlebox after irradiation may be related to the hippocampus abnormality, based on stress-arousal interpretation of hippocampal functioning in a situation employing noxious stimulation.

In avoidance conditioning in a two-way shuttle-box, avoidance performance of the jaundiced rats ( j j : n = 17) was inferior to that of the asymptomatic littermate controls (j/ + ), however, the correlations between the total serum bilirubin level and the number of avoidance responses in the jaundiced group was not significant. About 25% of the jaundiced rats were similar to the controls in avoidance performance, whereas about half of the jaundiced rats (n = 8) showed little or no avoidance response over trials. No significant defects in reflexes were observed in the jaundiced rats. Five out of 8 jaundiced rats with avoidance impairments showed tremor (oscillatory movements of the head and trunk) during exploratory behavior. Since the occurrence of tremor was attributable to severe cerebellar hypoplasia, this motor uncoordination might be due to bilirubin encephalopathy.

Gustatory avoidance studies normally focus on the diminished occurrence of a consummatory behavior as the primary dependent variable. Several reports have described behaviors which accompany this gustatory avoidance response but no attempt has been made to automate collection of such data. In the following studies lithium chloride (LiCl) was administered to rats following saccharin consumption in a standard gustatory avoidance paradigm. The rats also had the opportunity to make noncontingent target biting responses on an inanimate target. It was observed that there was a significant decrease in saccharin intake following its pairing with LiCl. High target biting rates were associated with this avoidance response and, to a lesser degree, with initial target exposure. These observations are discussed in terms of paradigm contingencies.

Previous studies which have examined the effects of lesions of the habenula on active avoidance learning have not provided unambiguous support for response deficits. Moreover, interpretation of early studies is confounded by large lesions which damaged adjacent structures. We report the effects of smaller circumscribed lesions of the habenula complex on a simple one-way active avoidance paradigm in three separate experiments in which the required operant was a step or jump onto an elevated platform. In the first study involving avoidance of shock of low intensity (0.5 mA) with an average long intertrial interval of 8 minutes, lesioned animals were not significantly different from sham operated controls. However, in following experiments in which stress levels were increased by raising the shock intensity and reducing the intertrial-interval, or in which the operant was made considerably more demanding by raising the height the animals had to jump to make an avoidance response, there were large lesion induced deficits in avoidance responding. The absence of significant differences between lesioned and sham operated controls in escape latencies suggested no lesion induced impairment of the response to the shock. It is suggested that the data not only support an effect of habenular lesions on active avoidance learning but also are consistent with a previous suggestion that the functional effects of lesion of the habenula on behaviour are effected through changes in dopaminergic function.

Eight pairs of spinal rats were exposed to an instrumental conditioning paradigm in which one animal served as the experimental and the other as a yoked control animal. An electrode, inserted into the experimental animal's foot, contacted an aqueous solution delivering shock to both animals. Leg flexion terminated the shock. Following two consecutive min without shock, the experimental animal's solution was raised an additional millimeter and training was re-instated. This procedure was repeated 4 times, or until the experimental animal failed to reach the 2 min criterion. In Run 1, one leg was trained; during Run 2, the contralateral leg was used. In addition, the animal which served as the experimental in Run 1 served as the yoked control in Run 2 and vice versa. The results indicate that the spinal rat is capable of acquiring successively higher criteria in an instrumental conditioning routine. In conjunction with previous results, these findings suggest that instrumental avoidance learning can occur in the spinal cord.

Male Sprague Dawley rats (n = 24), which received either bilateral electrolytic lesions, kainic acid lesions or sham treatments in the lateral habenula, were tested for acquisition of a one-way, conditioned avoidance response. Animals with electrolytic lesions failed to learn the avoidance task within 15 trials. In contrast, rats with kainic acid lesions performed as well as the control group. The results indicate that the disruption of the septal-medial habenula-interpenduncular nucleus pathway may be responsible for the observed avoidance deficit in electrolytically lesioned animals.

In the first experiment, it was demonstrated that a convulsion provoked from a kindled amygdala focus 10 min before a trial produced a state of dissociation for a one-trial inhibitory avoidance response. In the second experiment, it was shown that bilateral adrenalectomy alleviated the state-dependent recall deficit in the dissociation paradigm. This abatement of the dissociation was near total when the adrenalectomized animals received their training trial in the normal state and their test trial in the postconvulsive state; on the other hand, a significantly less satisfactory abatement was seen in adrenalectomized animals trained in the postconvulsive state but test in the normal state. The adrenalectomy had no effect on the evolution of the kindling or on the motor convulsion and AD, but did influence the weight gain. Kindling per se seemed to induce an adrenal hypertrophy effect.

The acquisition of a square-runway avoidance response was studied in rats with septal lesions The lesioned rats acquired the square-runway avoidance response significantly faster than the control rats. In a second experiment lesioned and control rats were compared on the acquisition of a regular one-way avoidance response in the same apparatus. This change in procedure facilitated the avoidance responding of the control rats and inhibited avoidance acquisition by the rats with septal lesions.

Single injections of either ACTH or lysine vasopressin (LVP) were administered to mice at one of three times: either (1) prior to training in a passive avoidance situation where the aversive stimulus is attack by a trained fighter mouse, (2) just following acquisition of the passive avoidance response, or (3) just prior to a first retention test at 24 hr after acquisition. Retention of the avoidance response also was assessed at 48 and 240 hr postacquisition. Both ACTH and LVP enhanced retention of the response, although their effects were different in character. ACTH's effects were relatively short-lived: the facilitatory effect of ACTH treatment was evident at the first (24 hr) retention test but had disappeared by the 240 hr test. On the other hand, LVP's effects became apparent later (at 48 hr) but lasted through the 240 hr test. In addition, the critical times for their administration were different: ACTH treatment enhanced avoidance retention no matter when the hormone was administered, whereas LVP only enhanced retention if this hormone had been administered after acquisition or prior to the first retention test; LVP treatment before acquisition did not affect avoidance-of-attack. The effects of ACTH and LVP on avoidance-of-attack are basically similar in form to the effects of these hormones on avoidance-of-shock.

The ability to maintain a conditioned avoidance response (CAR) was studied in normal Long-Evans rats and rats of the Brattleboro strain which were either homozygous or heterozygous for hereditary hypothalamic diabetes insipidus (DI). Homozygous DI rats had a lower CAR acquisition rate than did normal or heterozygous DI rats. However, the homozygous DI rats exhibited significantly greater CAR retention than did the other animals over the total period of extinction testing. The greater CAR retention could not be accounted for by either increased sensitivity to the electric foot shock used as the unconditioned stimulus or by perching on the metal center barrier of the training shuttle box, a form of behavior unique to the homozygous DI rats. Since the homozygous DI rat is totally lacking in hypothalamic antidiuretic hormone (ADH), the greater CAR retention of these animals indicates that ADH is not a requirement for CAR retention.

Age-related changes in learning ability were studied in senescence-accelerated mice (SAM) reared under specific pathogen-free (SPF) conditions. SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) showed an age-associated increase in spontaneous motor activity (SMA) compared with SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain) in a novel environment when the activity was measured in the light period, although there was no significant difference in the dark period. In observations of the circadian rhythm of SMA, SAM-P/8 showed a significant increase in diurnal SMA. In SAM-P/8 mice, the acquisition of passive avoidance response was slightly but significantly impaired even at 2 months of age, compared with SAM-R/1 control; the impairment became obvious with aging. In a one-way active avoidance task, SAM-P/8 did not show any impairment in the acquisition of avoidance response at 2 and 4 months of age. However, significant impairment was observed in SAM-P/8 at 12 months of age. The impairments of avoidance tasks were not due to a decrease in shock sensitivity, as indicated by no significant change in the flinch-jump threshold. In a water-filled multiple T-maze task, there was no difference in the number of errors between the two groups. With regard to the performance time to reach the goal, however, SAM-P/8 showed a mild prolongation at 2 months of age, and the prolongation became marked with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Exogenous elevation of circulating ACTH level facilitated the acquisition of a two-way avoidance response at a high but not at a moderate US intensity. Injections of ACTH had no general effect on spontaneous shuttling activity, escape behavior to light-onset, or intertrial responding during avoidance conditioning. Adrenalectomy, which resulted in minimal plasma levels of adrenocortical hormones and, presumably, elevated levels of ACTH, also facilitated avoidance responding. Injection of dexamethasone, a synthetic glucocorticoid and ACTH inhibitor, produced severe weight loss and hypophagia, but did not influence avoidance performance. However, the failure of dexamethasone to affect acquisition of avoidance responding was not related to its effect on body weight and food intake. The action of ACTH on avoidance conditioning is clearly extra-adrenal, but ACTH is not essential to normal performance, at least when high levels of glucocorticoids are present.

Intracerebral implantation of dexamethasone phosphate facilitated the rate of extinction of a pole jumping avoidance response when implanted into various areas in the median and posterior thalamus and in the ventriculus lateralis. Corticosterone, the rat's natural corticosteroid, also facilitated extinction of the avoidance response, but mainly if implanted in or near the nucleus parafascicularis. Implantations of either dexamethasone phosphate or corticosterone in other areas like hippocampus, nucleus septi lateralis, nucleus caudatus putamen, nucleus interstitialis striae terminalis and nucleus ventralis thalami did not result in a modification of the extinction rate.

The effect of the ACTH analogue ACTH 1–10 was studied on the rate of extinction of a pole jumping avoidance response in thyroidectomized rats with or without replacement therapy with 1-thyroxin. ACTH 1–10 appeared to delay the rate of extinction of the CAR in thyroidectomized rats in a similar way as in sham-operated animals. ACTH 1–10 was also active in thyroidectomized rats treated with thyroxin. The thyroxin treatment itself also caused a significant delay in the rate of extinction of the CAR. These results indicate that the inhibitory effect of ACTH analogues on the rate of extinction of the CAR is not mediated by the thyroid gland.

Sixty-three min or zero min of ESB was applied to two groups of cats through indwelling electrodes in the inferior colliculus. All animals were then trained to make an avoidance response with presentations of a 10 sec train of ESB serving as a conditioned stimulus. After reaching criterion on the conditioning task a psychophysical procedure was employed to track the 75 per cent detection threshold for ESB over several days. Those animals which had received ESB prior to training showed a stable threshold over test days. Animals which had not received the pretraining treatment showed a trend that was significantly different—a decline in threshold over test days. The data suggest that the observed differences in threshold reflected a change in sensitivity of the neural tissue as a result of the amount of time that the stimulating current had been applied to the tissue. An additional hypothesis concerning stimulation-bound behavior was described.

Double-walled cannulae were implanted in the septal region of sixteen cats. Injections of carbachol into dorsal midline septal placements significantly reduced the percentage of asymptotic, shuttle-box avoidance responses. Those animals demonstrating mild to moderate signs of overt behavioral change with carbachol were most impaired on the avoidance task. However, in contrast to the results for avoidance responses, the dorsal midline carbachol injections were found to significantly decrease the latencies of avoidance responses while norepinephrine increased avoidance response latencies. The production of overt behavioral effects and of shorter latency CARs with the dorsal midline carbachol injections was discussed in terms of the possibility that cholinergic neurons in the dorsal midline septal area may mediate certain aspects of behavioral activation, possibly via their influence on the hippocampus.

The involvement of several regions of the newly-hatched chick's forebrain in mediating a learned avoidance response was investigated. Ablations of the posterolateral portion of the telencephalon resulted in complete loss of retention and relearning of the task. Dorsomedial ablations that included parts of the hyperstriatal complex caused a deficit in new learning but not in the retention of a presurgically acquired experience. In contrast, frontal ablations impaired retention and relearning of a preoperatively learned response but did not affect acquisition in chicks initially trained after surgery. These and other findings suggest that telencephalic structures in birds and mammals presumed to share a common phylogenetic ancestry may play analogous roles in the behavior of the two classes.

Cats with restricted lesions placed in the mesial aspect of the lateral and posterolateral gyri (striate cortex) were trained in a Yerkes-Alley on a circle-square pattern discrimination, and then given acquisition and extinction training in a two-way active avoidance response (AAR) task. Additional groups of animals were first trained on the pattern discrimination and then operated and tested on the retention and relearning of the discrimination. The results show that these restricted striate cortical lesions do not disrupt acquisition, retention or the relearning of the visual discrimination, nor other types of observed visually-guided behavior, but do produce a severe acquisition deficit in the avoidance task. The results of this study confirm our previous findings that it is striate cortex and not the cingulate gyrus that produces AAR deficits following ablation. These results along with other recent neurophysiological data reporting that the striate cortex contains units responsive to non-visual stimuli suggest that in the cat visual cortex might mediate non-visual as well as visual functions.

The behavior of rats with either dorsal or ventral hippocampal lesions was compared to that of a control group in a series of tests. Dorsal hippocampal lesions made rats hyperactive in novel situations, did not affect rates of habituation, facilitated acquisition of a conditioned emotional response (CER), and retarded acquisition of a one-way active avoidance response. Ventral hippocampal lesions made rats hyperactive in novel situations, affected the rate of habituation of exploratory responses, retarded extinction of the CER, and tended to facilitate acquisition of the one-way active avoidance response. These results demonstrate that the dorsal and ventral hippocampus are functionally distinct. When applied to an examination of previous data, this differentiation may help to clarify present confusion about hippocampal function. Possible functions of the dorsal and ventral areas are discussed.

In the first set of experiments, we used groups of rats with either bilateral or unilateral ventral mesencephalic lesions and a group of controls in the following tests: diurnal exploratory activity, nocturnal activity, Skinner box and avoidance conditioning. Both groups of lesioned rats were found to be hyperactive in both types of activity tests, but those with unilateral lesions showed hyperactivity to a lesser extent. Neither of the experimental groups showed any evidence of extinction in the Skinner box. Rats with bilateral lesions learn a conditioned avoidance response more easily than the control animals but they also tend to show inadaptive behavior during the course of the testing procedure. In a second experiment, stimulating and recording electrodes were implanted in the lateral hypothalamus in certain of the animals of the three previous groups, having lesions as well. Such lesions were found to significantly decrease the threshold of arousal to central hypothalamic stimulation. From the results of our lesioning and testing procedures, a syndrome has been defined. However, the complex structure of the region that was destroyed does not permit a clear interpretation of the results.

Rats trained under unilateral cortical spreading depression on a brightness discrimination task for water reinforcement will show little or no transfer when retrained with the contralateral cortex depressed. The current study was performed in order to determine if the degree of transfer can be affected by reinforcement or motivational variables. Rats were trained on a brightness discrimination task to either escape or avoid painful foot shock. The animals trained to escape showed nearly perfect transfer. The animals trained to avoid showed very little transfer of the avoidance response but did transfer the brightness discrimination. It was concluded that in the unilateral spreading depression paradigm the degree of transfer obtained on similar tasks is altered by changing the reinforcement.

Twenty monkeys were trained on two main tests, 1 and 2. Test 1 included both a conditioned avoidance response (CAR) and a food reinforced response (FRR) according to a random schedule of presentation. Test 2 consisted of a standard test of delayed response (DR) made in WGTA. A bilateral ablation of the dorsal part of the premotor cortex has provoked significant deficits in Test 1. The CAR and the FRR were unequally and differently affected according to the individual differences. The animals did not show the phenomena called by some authors the cue magneto reactions. They also did not show deficits in Test 2, (DR), nor any disturbances of the spontaneous locomotor activity or the orienting responses to neutral stimuli.

Learning of a conditioned avoidance response (CAR) in the shuttle box was studied in rats with lesions in the fimbria-fornix region. Lesioned rats showed facilitation in the acquisition of the CAR, accompanied by a lowered level of freezing responses and a higher level of intertrial activity. At shorter CS-UCS intervals lesioned rats showed better performance than controls. When measured in an activity box, a statistically significant increase in the spontaneous activity of lesioned animals was found. No increase in activity was observed, however, when the lesioned animals were tested in a linear maze. No changes in emotionality were found.

The presence of severely restricted environmental conditions reported to produce marked alterations in sleep patterns, most notably REM sleep, had no effect upon the acquisition and the consolidation of a conditioned avoidance response in rats. However, those subjects who learned the response in the severely restricted environment showed a marked decrement in avoidance responding when retested from normal conditions. The reestablishment of the severely restricted environment was a sufficient condition for the return of performance during retest situations. Other environments produced no such effects. The correlation between changes in sleep behavior and performance was greater than the correlation between environment and performance. There is some factor (or factors) present in such environmental situations that manifests itself in two ways: external changes in sleep patterns and the development of a factor performance coupling. It is not known whether both phenomena share a common origin or whether they are independent events. The development of an environmental state dependency provides one possible explanation for some of the behavioral alterations seen following sleep-cycle disruption. The utilization of other techniques capable of influencing sleep is necessary to determine the factors relevant, in this environment, to the production of the changes noted.

Rats were trained to perform a conditioned avoidance response (conditioned stimulus—light; unconditioned stimulus—electric shock) with bilateral sensory input and in conditions allowing the major component of either or both the relevant sensory stimuli to be directed to one cerebral hemisphere. Subsequent application of spreading depression to either hemisphere in the case of bilaterally trained animals or to the hemisphere receiving the sensory input (‘trained’ hemisphere) after unilateral training gave rise to a drastically impaired performance. Performance was also impaired when the hemisphere not receiving the sensory input (‘untrained’ hemisphere) was depressed though not to the same extent. The differential effect of depressing the “trained” and “untrained” hemispheres was quantitatively dependent upon whether neither, either or both the sensory inputs were lateralized.

Parasagittal surgical cuts in the medial quadrant of the lateral hypothalamus which isolated the medial half of the hypothalamus from all lateral connections produced marked deficits in avoidance learning but no discernible change in performance on a test of intra-species aggression. The animals showed transient motor deficits as well as aphagia and adipsia but were normal on all measures before the avoidance training and aggression tests were begun. Similar parasagittal cuts lateral to the lateral border of the anterior and medial hypothalamus (including the region lateral to the ventromedial nuclei) facilitated the acquisition of a shuttle box avoidance response but failed to affect intra-species aggression. These animals were aphagic and adipsic for longer periods of time but had recovered normal body weights and motor abilities at the time of testing.

In a self-selection situation, rats performing a discriminated shock avoidance task increased their intake of ethanol significantly when unavoidable random shock signalled by a warning light was simultaneously delivered. During the control shock avoidance period or when non-cued unavoidable shock was delivered, the animals exhibited their normal aversion to ethanol. As a result of these findings, a differentiation was made between two kinds of stressors: the behavioral stress of cued random unavoidable shock (punishment) and/or the physical stress of non-cued unavoidable shock. For the first time a relationship has been established in animals between a so-called psychological stressor and the volitional selection of ethanol.

Female rats acquired an active avoidance response more rapidly than males, while males were more efficient than females in a passive-avoidance situation. Females showed a higher level of activity than males. Also they showed a higher frequency of intention movements and grooming activity during the retention tests after receiving one trial foot-shock. Possible relations between general activity and differential performance in learning tasks are discussed.

Rats have been trained on a simple conditioned avoidance response to light after undergoing unilateral ablation of the striate cortex. On completion of training, the ability of each eye alone to mediate the response has been tested. The eye ipsilateral to the cortical ablation maintains performance well, but with the contralateral eye performance is significantly impaired. With repeated testing of each eye separately, the performance with the contralateral eye shows gradual improvement so that the inter-eye difference ultimately becomes insignificant. Performance with the contralateral eye is better preserved, to a significant extent, if it is tested immediately after the ipsilateral eye than when this order is reversed. The results have been discussed in terms of the differences in central representation of the conditioned avoidance response to light at cortical and subcortical levels.

Rats treated intracisternally with multiple doses of 6-hydroxydopamine (2 × 200 μg) in combination with pargyline, which depleted both brain norepinephrine and dopamine, showed no evidence of acquisition of an avoidance response in the shuttle box. Mean intertrial interval (ITI) crosses were not significantly different from control. Treatment with 2 × 250 μg of 6-hydroxydopamine without pargyline also retarded acquisition of avoidance, but to a lesser extent. ITI crosses for this latter group were significantly increased. Preferential depletion of norepinephrine facilitated acquistion of avoidance and increased the number of ITI crosses. The rate of acquisiton of the avoidance response by rats in which dopamine was preferentially reduced was not significantly different from control animals even though ITI crossing was significantly increased. These results are discussed in relation to views concerning the role of brain catecholamines in avoidance responding.

In a discriminated shock avoidance situation, rats offered a choice between water and ethanol increased their ethanol consumption significantly during acquisition of the avoidance response and when random unavoidable shock signaled by a warning light was simultaneously delivered. Control rats which received unsignaled random unavoidable shock during the avoidance sessions, and controls which received only signaled or unsignaled random unavoidable shock did not increase ethanol consumption. A trend toward increased levels of plasma corticosterone was found in the experimental rats over control animals. Weights of the thymus and adrenal glands did not differ significantly between the experimental and control groups. A relation was observed between ethanol consumption and changes in the stimulus conditions which required the acquisition of a new response.

Brief deprivation of REM sleep (REMD) immediately following inhibitory avoidance training abolished negative transfer in an active avoidance situation without impairing retention of the inhibitory avoidance response. REMD beginning 3 hr after inhibitory training had no effect. A reminder treatment (brief placement in the apparatus) between 30 min and 24 hr before active avoidance training counteracted the REMD impairment of negative transfer. The reminder treatment was not impaired by subsequent REMD.

Eight pigs were trained in a shuttle-box to avoid electric shocks according to a continuous avoidance schedule. After stabilisation of the response rate they were submitted to a discriminative Pavlovian fear conditioning. In a subsequent test session, presentation of the CS+ increased the avoidance response rat at a greater extent than the CS−. Dexamethasone (0.2 mg/kg) administered before Pavlovian conditioning and before test sessions enhanced the increase in avoidance response rate to both CS presentation, irrespective of its type. Results are interpreted in terms of DX effects on response inhibition processes.

In these experiments, we examined the prolactin (PRL) response during the acquisition of a conditioned avoidance response (CAR). Rats were tested daily in a two-way shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial period, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a CAR. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. PRL levels increased during early acquisition testing, when the rats had not learned to avoid the shock. After one week of testing, acquisition performance increased considerably (70% CARs) while PRL levels remained unchanged. Thus, we were able to show that as rats learned to modify their behavior in response to a stressful situation, they could also modify their PRL response to the stressor.

Albino rats were trained in a conditioned avoidance response and tested 48 hr later for retention in a 2 × 2 factorial design of alcohol and no alcohol states. Group AA was trained and tested 1 hr after a stomach-tubing of an 11.88% aqueous solution of ethanol in an amount which was approximately 2% of the animal's bodyweight. Group OO was trained and tested without alcohol. (Group AO received alcohol in testing, but not in training.) Analysis of variance of the difference scores between training and testing percent avoidances showed an alcohol effect, as well as an interaction of the alcohol effects in the two situations. The results are discussed in relation to the central nervous effects of ethanol.

Rats trained to perform a free-operant wheel-turn avoidance response had gastric lesions but their yoked controls did not. This constitutes a replication of Brady's ‘Executive’ ulcer experiment but with random assignment of animals to conditions and demonstrates that a free-operant avoidance schedule is ulcerogenic.

Sprague-Dawley rats received training in a modified version of the Noble-Collip tumbling apparatus under a regime designed to produce resistance to this form of trauma. These animals were then subjected to a procedure in which X-irradiation was paired with saccharin solution. This procedure typically results in a subsequent conditioned avoidance response of saccharin solution. Trauma resistant rats showed a significantly lessened avoidance response when compared to the appropriate controls. It is suggested that resistance to tumbling trauma served to mitigate the effects of X-irradiation, thus accounting for the lessened saccharin avoidance responses.