Escape-avoidance Behavior Research Articles

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats.

Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days. Daily oral administration of 200 mg/kg NR beginning 7 days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape-avoidance behaviors. These effects were sustained after a 2-week washout period. This dose of NR increased blood levels of NAD by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape-avoidance behaviors. Pretreatment with 100 mg/kg oral acetyl-L-carnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt escape-avoidance behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD, a critical cofactor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. Because NR is a vitamin B3 precursor of NAD and a nutritional supplement, clinical tests of this hypothesis may be accelerated.

Turning Pain Into Cues for Goal-Directed Behavior: Implementation Intentions Reduce Escape-Avoidance Behavior ona Painful Task.

Pain automatically elicits escape-avoidance behavior to avert bodily harm. In patients with chronic pain, long-term escape-avoidance behavior may increase the risk of chronic disability. The aim of the presents study was to examine whether implementation intentions reduce escape-avoidance behavior during painful tasks in healthy individuals. Implementation intentions are "if-then" self-statements associating situational cues with goal-directed behaviors. Seventy healthy participants performed a painful finger pressing task, preceded by either implementation intention instructions with pain or a nonpain cue as a cue for goal-directed behavior, or control instructions. Escape-avoidance behavior was operationalized as task duration and response rate. Inhibitory control was measured using the Stop Signal Task. The pain implementation intentions resulted in the longest task duration (P=.02), and thus less escape-avoidance behavior. Low inhibitory control was associated with shorter task duration (P=.03), and thus more escape-avoidance behavior. The nonpain implementation intentions resulted in the highest response rate, but only when inhibitory control was low (P=.04). Implementation intentions referring to pain or nonpain reduce escape-avoidance behavior on a painful task. It is worthwhile to examine whether individuals in pain and with low inhibitory control benefit from interventions that incorporate implementation intentions. To our knowledge, this study is the first to show that forming implementation intentions reduces escape-avoidance behavior during pain and fosters nonpain goal pursuit. The use of implementation intentions is indicated to be an intervention that could be of use in patients with pain, particularly when inhibitory control is low.

Assessment of avoidance behaviors in mouse models of muscle pain

Pain encompasses both a sensory as well as an affective dimension and these are differentially processed in the cortex. Animal models typically use reflexive behaviors to test nociceptive responses; these are thought to reflect the sensory dimension of pain. While several behavioral tests are available for examining the affective dimension of pain it is unclear if these are appropriate in animal models of muscle pain. We therefore tested the utility of existing paradigms as well as new avoidance paradigms in animal models of muscle pain in mice. Specifically we used an escape-avoidance test to noxious mechanical stimuli, a learned avoidance test to noxious mechanical stimuli, and avoidance of physical activity. We used three animal models of muscle pain: carrageenan-induced inflammation, non-inflammatory muscle pain, and exercise-enhanced pain. In the carrageenan model of inflammation mice developed escape-avoidance behaviors to mechanical stimuli, learned avoidance to mechanical stimulation and avoidance of physical activity – these models are associated with unilateral hyperalgesia. When both muscles were inflamed, escape-avoidance behaviors did not develop suggesting that equivalent bilateral pain behaviors cannot be tested with an escape-avoidance test. In the non-inflammatory muscle pain model mice did not show significant changes in escape-avoidance behaviors or learned avoidance, but did avoid physical activity. In the exercise-enhanced pain model, there were no changes in escape-avoidance, learned avoidance of noxious or physical activity In conclusion, we developed several testing protocols that assess supraspinal processing of pain behaviors in models of muscle pain and that are most sensitive in animals with unilateral hyperalgesia.

Amygdala involvement in human avoidance, escape and approach behavior

Many forms of psychopathology and substance abuse problems are characterized by chronic ritualized forms of avoidance and escape behavior that are designed to control or modify external or internal (i.e., thoughts, emotions, bodily sensations) threats. In this functional magnetic resonance imaging investigation, we examined amygdala reactivity to threatening cues when avoidance responding consistently prevented contact with an upcoming aversive event (money loss). In addition, we examined escape responding that terminated immediate escalating money loss and approach responding that produced a future money gain. Results showed cues prompting avoidance, escape and approach behavior recruited a similar fronto -striatal-parietal network. Within the amygdala, bilateral activation was observed to threatening avoidance and escape cues, even though money loss was consistently avoided, as well as to the reward cue. The magnitude of amygdala responses within subjects was relatively similar to avoidance, escape and approach cues, but considerable between-subject differences were found. The heightened amygdala response to avoidance and escape cues observed within a subset of subjects suggests threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance–coping in various clinical disorders. Further assessment of the relation between amygdala reactivity and avoidance–escape behavior may prove useful in identifying individuals with or at risk for neuropsychiatric disorders.

Psychometric Properties of a Korean Version of the Pain Anxiety Symptoms Scale-20 in Chronic Pain Patients

The Pain Anxiety Symptoms Scale (PASS-20) consists of 20 items designed to assess four aspects of pain-related anxiety: cognitive anxiety, escape-avoidance behaviors, fear of pain, and physiological symptoms of anxiety. Although the PASS-20 is a well-established measure of pain-related anxiety in Western samples, different cultures may yield a different factor structure or different associations with pain-related outcome variables. The purposes of this study were (1) to examine the factor structure of a Korean language version of the PASS-20 (KPASS-20); (2) to examine reliability and construct validity of the KPASS-20; and (3) to compare the findings of this study with those of the original psychometric study using a Western sample. A total of 166 patients seeking treatment in a university pain management center located in Seoul, Korea participated. Results indicated that the KPASS-20 consists of three factors, "fearful thinking," "physiological response," and "avoidance," and has adequate reliability and construct validity estimates. On the mean total score of the KPASS-20, the Korean sample had a significantly higher score than the original Western sample. In addition, in correlation analyses between the total score of the KPASS-20, physical functioning, and pain severity, the Korean sample had significantly higher coefficients, whereas similar differences were not found in the analyses of psychological functioning and depression. The findings provide preliminary support for the reliability and validity of the KPASS-20.

Naltrexone fails to increase pain affect in response to inflammatory pain in a novel escape/avoidance paradigm

The non-specific opioid antagonist naltrexone has traditionally been used as treatment for opioid overdose, as well as in research settings as an antagonist to examine opioid and non-opioid mediated analgesia. However, the mechanisms by which this drug operates are not well understood, and its exact effects on sensory and affective pain processes remain uncertain. Various studies have demonstrated that naltrexone behaves in a paradoxical manner, leading to analgesia, no discernable changes, or an increase in pain, depending on the circumstances of the study. This imprecise spectrum of effects leads to difficulty in interpreting results in studies where naltrexone was utilized as an antagonist. Therefore, the purpose of this experiment was to further examine whether naltrexone elicits dose-dependent effects in behavioral tests designed to quantify the sensory and affective components of pain. Naltrexone was not expected to have an effect on carrageenan-induced inflammatory pain in sensory pain measures, but a dose-dependent increase was predicted in behavior related to the affective component of pain. Eighty-eight male Sprague–Dawley rats were used to test these hypotheses by measuring Mechanical Paw Withdrawal Thresholds before and after naltrexone injection and by assessing performance in the Place Escape Avoidance Paradigm test, a novel paradigm to test pain affect, in which naltrexone had not been utilized. The results demonstrated that naltrexone failed to increase place/escape avoidance behavior as anticipated, but rather produced a slight, but non-significant, decrease in escape avoidance behavior. Further research is needed to elucidate the differential effects of naltrexone on various aspects of pain-related behavior.

Quantitative Comparisons of the Acute Neurotoxicity of Toluene in Rats and Humans

The behavioral and neurophysiological effects of acute exposure to toluene are the most thoroughly explored of all the hydrocarbon solvents. Behavioral effects have been experimentally studied in humans and other species, for example, rats. The existence of both rat and human dosimetric data offers the opportunity to quantitatively compare the relative sensitivity to acute toluene exposure. The purpose of this study was to fit dose-effect curves to existing data and to estimate the dose-equivalence equation (DEE) between rats and humans. The DEE gives the doses that produce the same magnitude of effect in the two species. Doses were brain concentrations of toluene estimated from physiologically based pharmacokinetic models. Human experiments measuring toluene effects on choice reaction time (CRT) were meta-analyzed. Rat studies employed various dependent variables: amplitude of visual-evoked potentials (VEPs), signal detection (SIGDET) accuracy (ACCU) and reaction time (RT), and escape-avoidance (ES-AV) behaviors. Comparison of dose-effect functions showed that human and rat sensitivity was practically the same for those two task regimens that exerted the least control over the behaviors being measured (VEP in rats and CRT in humans) and the sensitivity was progressively lower for SIGDET RT, SIGDET ACCU, and ES-AV behaviors in rats. These results suggested that the sensitivity to impairment by toluene depends on the strength of control over the measured behavior rather than on the species being tested. This interpretation suggests that (1) sensitivity to toluene would be equivalent in humans and rats if both species performed behaviors that were controlled to the same extent, (2) the most sensitive tests of neurobehavioral effects would be those in which least control is exerted on the behavior being measured, and (3) effects of toluene in humans may be estimated using the DEEs from rat studies despite differences in the amount of control exerted by the experimental regimen or differences in the behaviors under investigation.

Behavioral Training for Increasing Preschool Children's Adherence With Positive Airway Pressure: A Preliminary Study

Behavioral training was implemented to increase adherence with positive airway pressure (PAP) in 4 preschool children. The training employed distraction, counterconditioning, graduated exposure, differential reinforcement, and escape extinction. A non-concurrent multiple baseline experimental design was used to demonstrate program effects. Initially, the children displayed distress and escape–avoidance behavior when PAP was attempted. With training, all 4 children tolerated PAP while sleeping for age appropriate durations. For the 3 children with home follow-up data, the parents maintained benefits. The results are discussed in relation to behavior principles, child health, and common barriers to PAP adherence.

Sex Differences in the Effects of Neuroleptics on Escape-Avoidance Behavior in Mice: A Review

The literature of the effects of dopamine antagonists on escape-avoidance, focusing on data obtained in our laboratory with male and female mice, is reviewed. The acute administration of haloperidol, raclopride, clozapine, and SCH 23390 impaired escape-avoidance behavior more in males than in females, and the subchronic administration of haloperidol had a similar effect. This appeared to be a reliable phenomenon, because it was observed in both kinds of administration, in two mouse strains, and with several drugs and doses. The observed results were dose dependent, although the dose–effect relationship was not the same in all drugs. The sex differences in escape avoidance did not seem related to sex differences in the well-known deteriorating effects of these drugs on motor activity. In addition, an analysis of all our studies showed that there were no sex differences in the variability of responses, reinforcing the idea that female subjects should be included in these types of studies.

Gender differences in escape-avoidance behavior of mice after haloperidol administration

Gender differences in the disruptive effects of haloperidol on some reinforced behaviors have been observed in different species. However, the inhibitory action of haloperidol on the acquisition and performance of escape-avoidance behavior has only been investigated in male subjects. The present experiment was designed to investigate possible gender differences in the effects of haloperidol on the initial phase of an escape-avoidance learning task. Male and female mice of the OF1 strain were given a single training session in a shuttle-box. Thirty minutes prior to the behavioral test, mice were injected IP with haloperidol (0.25 mg/kg) or physiological saline (10 ml/kg). Latencies of escape and avoidance responses and the number of nonresponses, escapes, avoidances, pseudoavoidances, crossings during the adaptation period, and crossings during intertrial intervals (ITIs) were evaluated. The disruptive action of haloperidol on the escape-avoidance behavior of the mice was greater in males than in females. The number of nonresponses were higher and the number of escapes lower in treated males than in their female counterparts. These gender differences were not found in control subjects. Activity measures of spontaneous motor behavior (crossings in the adaptation period and during ITIs) did not present gender differences either. Several possible mechanisms responsible for this greater susceptibility of males to the inhibitory effects of haloperidol on escape-avoidance learning are discussed, especially the modulating role of female hormones on dopaminergic activity.

A Comparison of How Gifted/LD and Average/LD Boys Cope with School Frustration

Gifted/LD and Average/LD middle school boys in grades six through nine were compared on the ways they cope with difficult school situations. Both groups completed the Coping Resources Inventory (CRI). The students were then interviewed individually and asked to share how they handled the situations presented in four scenarios. The scenarios depicted difficult school situations which learning disabled students often face. The situations included difficulty with testing even when the information is “known,” inability to organize oneself, slow reading rate, and problems with handwriting. Students were also asked to rate their success in handling these situations. The interviews were taped and transcribed, the responses were then coded. Profile Analysis was used to analyze the CRI data, a MANOVA was used to compare coping strategies, and Chi Square to compare how they felt they handled the scenarios. No differences were found on the CRI. Significant differences were found in the actual strategies the groups reported using to cope with school difficulties. The gifted/LD students reported significantly more Planful Problem Solving, while the average/LD group reported more Distancing, Escape Avoidance behaviors, and Helplessness. There were no differences in the groups' reported feelings of success in coping. Recommendations were made for the direct teaching of Coping Strategies, Parental Involvement and Counseling Programs.

Effects of subchronic soman on avoidance-escape behavior and cholinesterase activities

Male Sprague-Dawley rats were trained on a discriminated avoidance-escape task. They were administered subchronically saline, 12.7 μg/kg (0.125 LD 50) soman, or 25.5 μg/kg (0.25 LD 50) soman. Injections were given 5 days per week for 4 weeks. Injections were given subcutaneously immediately following the avoidance behavior test session. Soman produced a reduction in avoidance behavior efficiency in a dose dependent manner. When soman was discontinued, the rats recovered their pre-soman control baselines. Untrained rats given soman according to the same soman regimen were used to measure acetylcholine in brain and cholinesterase activities in brain, blood, and diaphragm. After 18 soman injections at 12.7 and 25.5 μg/kg acetylcholine was reduced significantly only in the amygdala. Blood cholinesterase was inhibited as much as 57% after 12.7 μg/kg soman and 74% after 25.5 μg/kg. Plasma cholinesterase was inhibited to 24% by the 12.7 μg/kg dose of soman and to 38% by the 25.5 μg/kg dose. Plasma cholinesterase recovered to control levels 11 days after cessation of soman, and whole blood cholinesterase recovered 25 days after cessation of the higher soman dose. Cholinesterase was inhibited significantly in the hippocampus and amygdala in a dose dependent manner. The cholinesterase activities appear to parallel the soman induced decrement in avoidance behavior and the subsequent recovery to control levels following withdrawal of soman.

Effects of subchronic administration of soman on acquisition of avoidance-escape behavior by laboratory rats

Holtzman male Sprague-Dawley rats were given four injections of saline or soman at 31 μu/kg or 46 μ/kg. The injections were given every 3 days during a 2-week period. Tail vein blood samples, drawn 24 hr before the first injection and 24 hr after the last injection, were analyzed for acetylcholinesterase (AChE) inhibition. For the low and high soman groups, whole blood AChE was inhibited 20 and 24%, respectively, while plasma AChE was inhibited 17 and 25%, respectively. Parallel saline injections produced a small inhibition of whole blood AChE and an increase in activity (negative inhibition) of plasma AChE. During the second week of soman administration rats began training on a discriminated shock avoidance task. The seven animals administered 46 μg/kg soman did not learn the lever-pressing avoidance response during a period of 120 days. Five of eight saline rats and four of seven 31 μg/kg soman rats learned the avoidance response. There was no significant difference between learners relative to rat of learning of the avoidance task. All of the rats learned to escape the shocks. These data indicate that subchronic soman inhibits learning of new behaviors by laboratory rats.

Motor debilitation, short- and long-term shuttlebox deficits, and brain monoamine changes following footshock pretreatment in rats

Male hooded rat triplets, each consisting of an unshocked control (C), an animal that could escape from the shock by leverpressing (LE), and a yoked animal that received noncontingent shock (NC), were pretreated with either short-duration, high-intensity (Hi) or long- duration, low-intensity (Lo) footshock. Varying degrees of motor debilitation not offset by the escape contingency were apparent immediately following the Hi pretreatment. Only the rats showing motor debilitation had short-term deficits in FR-1 and FR-2 escape-avoidance performance that were related to lowered diencephalic norepinephrine (NE) levels. The Lo pretreatment, which utilized shocks ⩾5.0 sec in duration, had no significant long-term effects on escape-avoidance behavior under the conditions of this study. Only nondebilitated NC rats from the Hi pretreatment condition showed a reliable deficit in FR-2 shuttlebox performance at 72 h. This occurred in spite of the fact that their pretreatment shocks were shorter than 5.0 sec in duration and that they showed no signs of motor debilitation and essentially normal brain NE levels at 30 min.

Effects of chronic exposure to stressors on avoidance-escape behavior and on brain norepinephrine.

A single exposure to a severe stressor (either cold swim or inescapable shock) impairs subsequent performance in a shuttle avoidance-escape task (1), a deficit attributed to reduction in brain noradrenergic activity produced by these stressors. In the present paper, two experiments are described which examine how repeated exposure to such stressors affects (a) shuttle avoidance-escape performance (Experiment 1), and (b) aspects of brain norepinephrine metabolism (Experiment 2). Experiment 1 showed that, whereas subjects receiving the single exposure to cold swim or shock showed a large avoidance-escape deficit, subjects that received repeated exposure to these stressors for 14 days performed similarly to the control group that received no stressor. Experiment 2 showed that, whereas subjects that received one session of the inescapable shock stressor showed a lower level of norepinephrine in hypothalamus and cortex than did subjects that received no shock, subjects that received repeated exposure to inescapable shock or cold swim showed neurochemical "habituation." Subjects that received repeated shock showed elevated tyrosine hydroxylase activity and no depletion of norepinephrine level, and both repeated shock and cold swim caused a decrease in uptake of 3H-norepinephrine by slices of cortex in vitro. Thus, it is concluded that the behavioral and neurochemical changes that were observed after the stressful conditions studied are consistent with the hypothesis that changes in avoidance-escape responding following exposure to these stressful events are due to changes in brain noradrenergic activity.

Monamines as mediators of avoidance-escape behavior.

A series of three experiments were carried out to test the hypothesis ("motor activation deficit" hypothesis) that the avoidance-escape deficits observed following certain highly stressful conditions result from changes in activity of noradrenergic (or other monominergic) neural systems. These studies indicate that: (1) Depletion of monamines by a single injection of tetrabenazine produces an active avoidance-escape deficit when the avoidance-escape response involves a relatively high degree of motor activity but not when a minimum of motor activity is required. This parallels results found when animals are acutely exposed to a stressor prior to avoidance-escape testing. (2) Daily injections of tetrabenazine for a period of two weeks, like daily exposure to inescapable shock for the same period of time, markedly attenuates the magnitude of the avoidance-escape deficit produced by either a single injection of tetrabenazine or single session of inescapable shock. (3) Decreasing the stress-induced depletion of monamines by the use of an MAO inhibitor serves to protect the animals from the effects of inescapable shock, markedly reducing the avoidance-escape deficit produced by such shock. It is concluded that these results are consistent with the motor activation deficit hypothesis.

Effects of acute exposure to stressors on subsequent avoidance-escape behavior.

This paper attempts to show that severely stressful conditions can lead to a deficit in avoidance-escape responding by reducing noradrenergic activity in the brain. It is argued that this stress-induced neurochemical change explains more adequately an avoidance-excape deficit seen previously in dogs after severe inescapable shock than does the "learned helplessness" explanation originally offered for this effect. A series of six experiments are described that test the stress-neurochemical change explanation, which is called the "motor activation deficit" hypothesis. The first experiment showed that a brief exposure to cold swim, which reduced central noradrenergic activity but did not induce "learned helplessness," produced an avoidance-escape deficit similar to that observed after inescapable shock in the original "learned helplessness" studies. Subsequent experiments demonstrated that the deficit induced by cold swim was also similar to the original deficit in that it too dissipated with the passage of time and was reduced by pretraining animals in the correct response. Further experiments then showed that the deficit induced by cold swim was (a) aggravated by raising the height of the barrier between compartments in the shuttle box, and (b) did not occur if the avoidance-escape task used required little motor activity, both of the findings being predicted by the "motor activation deficit" hypothesis. Finally, an avoidance-escape deficit was produced by inescapable shock, and it was found that this stressor likewise did not impair avoidance-escape responding if the task required little skeletal activity, a result not predicted by the "learned helplessness" hypothesis. The paper concludes by discussing how the results presented in this paper, as well as in succeeding papers, support the "motor activation deficit" explanation for certain avoidance-escape deficits, defining the cases to which the explanation applies and discussing the neurotransmitters involved.

Reinforced practice and reduction of different kinds of fears in adults and children

The purpose of this study was to determine whether or not fears with different origins, course and chronicity could be reduced by a common treatment program. A number of therapeutic procedures that had been experimentally demonstrated to be individually important in prior behavior modification studies with neurotic disorders were combined into a single therapeutic program called ‘reinforced practice.’ The combined elements were: graduated and repeated practice in approaching actual phobic stimuli: reinforcement for gains in performance; feedback of measurable progress; and instructions designed to arouse expectations of gradual success. In each of four experiments involving four different fears, namely fear of heights, snakes and electric shock in adults, and fear of darkness in young children, Ss who expeienced the ‘reinforced practice’ procedure improved their performance by a significant and substantial margin as compared to untreated control Ss. These results suggest that regardless of different etiologies, regardless of whether or not the fears are ‘rational’ or ‘irrational,’ and regardless of whether or not the fears are transitory or long lasting, the same treatment procedure can be equally effective in reducing escape-avoidance behavior.

Studies in genotype-environement interaction. I. Methodology and preliminary multivariate analysis of a diallel cross of eight strains of rat.

Previous studies concerned with genotype-environment interaction in behavior are discussed from methodological and gene-action points of view. A number of methodological advances have been made recently. In particular, designs introducing environmental variables factorially into standard genetic designs are extremely powerful. It is evident that all the methods appropriate to the analysis of factorial designs may be employed to investigate the interaction between such macroenvironmental variables and genotype. The main advantage of adopting such designs in psychogenetic studies is that much more complex behaviors may be investigated. Studying the gene-action controlling behavior as a means of increasing our understanding of its adaptive and evolutionary significance has been the aim of a number of recent psychogenetic studies. This approach applied to studies of genotype-environment interaction makes investigating the adaptive significance of these complex behaviors possible. A number of previous interaction studies are discussed from this viewpoint. The general finding is that gene action ensures that the hybrid genotypes, typical of natural populations, are buffered against environmental treatments aimed at producing deleterious and disruptive effects. However, an interesting study by Henderson, where the treatment was aimed at enrichment of the environment, revealed no such buffering effect. Instead, an increase in the range of inherited individual differences was found, differences which remained hidden in the control group. The main purpose of this report is to present findings of a replicated diallel cross of eight strains of rats employing an environmental treatment designed to investigate genotype-environment interaction. One group was subjected to infantile stimulation by early handling, and a control group was not handled. The principal measures taken in adulthood were open-field ambulation and defecation, two escape-avoidance behaviors, and body-build index. A preliminary analysis, employing a multivariate extension of Hayman's analysis of variance, is carried out describing the main findings. Each of the five measures in the analysis is shown to be under substantial independent genetic control, although a number of interesting interrelationships also emerge. Many interactions with stimulation are indicated for all measures. It is concluded that each measure should be subjected to a univariate analysis.

Effects of ribonuclease on acquisition and retention of escape-avoidance behavior in a selectively bred rat strain

Before and during the acquisition of escape-avoidance behavior, ribonuclease was administered to rats of a strain selectively bred for high rates of avoidance conditioning. In two replications of the experiment, it was found that the animals injected with 0.01-gm/kg ribonuclease in saline for 7 days before the behavioral testing was undertaken did not show any appreciable acquisition of the conditioned response, whereas the animals injected with the same dosage 7 days before testing as well as during 7 days of training acquired the response, starting the fourth day of training; on the seventh day, these animals were not any different from the control groups, which went through the same procedure except that only saline injections were administered.