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Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and adults.

The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PND 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.

Administration, Inhalation↗

Dissociation of recognition memory and associative learning by a restricted lesion of the chick forebrain.

Bilateral lesions of a restricted part of the chick forebrain (IMHV) have been shown to impair the acquisition and retention of imprinting preferences. The present study sought to determine the effects of such lesions on an operant conditioning task in which the reward was the presentation of one of two conspicuous objects, a stuffed jungle fowl or an illuminated red box. Twelve hours after hatching 28 domestic chicks received bilateral lesions of IMHV. Thirty-two chicks served as sham-operated controls. On the following day all birds underwent two sessions of operant training. After the second session the chicks were given a preference test. In this test the reinforcing object (box or fowl) and a novel object (fowl or box, whichever had not been seen before) were simultaneously presented. One test was given 2 hr and a second 24 hr after the termination of the operant task. The lesioned birds were not impaired on the operant task or on measures of general activity. In contrast, these birds failed to show a preference for the reinforcing object whereas the sham-operated controls strongly preferred this object. These results suggest that object recognition and associative learning can be dissociated in young chicks. This dissociation is reminiscent of certain human amnesias. The lesion did not impair an expected increase in preference for the stuffed fowl which developed in all birds between the 2-hr and 24-hr preference tests.

Animals↗

Behavioral evidence for competing motivational drives of nociception and hunger.

Homeostasis, an organisms' tendency to maintain a healthy balance of the physiological state of the body, is necessary for survival. Hunger induces a motivational state to consume food. Recently, pain has been referred to as a homeostatic emotion similar to hunger or thirst in that animals are motivated to respond in a certain way that may increase their chance of survival. Therefore, the purpose of the present experiment was to examine behavior in rodents during two competing homeostatic/motivational drives (i.e., hunger and formalin pain). During the first phase of the formalin test, animals displayed typical responsiveness to the inflammatory condition and completed fewer chains for food reinforcement as compared to the baseline session. However, during the second phase of the formalin test, animals showed decreased nociceptive behavior compared to formalin-injected animals that were not trained in the operant conditioning paradigm. During this phase, the trained animals exhibited maximal responsiveness for food reinforcement. These results demonstrate that the engagement of behaviors reflecting motivational drives to restore homeostasis depends on the intensity or degree of imbalance of the competing drives. More specifically, animals are motivated to attend to one state of imbalance at a time.

Animals↗

Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory.

Mice were trained on a variety of odor detection and discrimination tasks in 100- or 200-trial sessions using a go, no-go discrete trials operant conditioning procedure. Odors, presented for 1 s on each trial, were generated by an air dilution olfactometer (for threshold tests) and an easily constructed eight-channel liquid dilution unit (for two- and multiple-odor discrimination tasks). Mice rapidly acquired the operant task and demonstrated excellent stimulus control by odor vapors. Their absolute detection threshold for ethyl acetate was similar to that obtained with rats using similar methods. They readily acquired four separate two-odor discrimination tasks and continued to perform well when all eight odors were presented in random order in the same session and when reinforcement probability for correct responding was decreased from 1 to 0.5. Memory for these eight odors, assessed under extinction after a 32 day rest period, was essentially perfect. Time spent sampling the odor on S+ and S- trials was highly correlated with response accuracy. When accuracy was at chance levels (e.g. initial trials on a novel task), stimulus sampling time on both S+ and S- trials was approximately 0.5-0.7 s. As response accuracy increased, sampling time on S+ trials tended to increase and remain higher than sampling time on S- trials.

Acetates↗

Environmental and interoceptive influences on chronic low back pain behavior.

The operant conditioning theory states that environmental stimuli greatly influence chronic pain behavior. In contrast, the hypochondriasis theory states that pain behavior is the result of an intensified pain perception which is part of a more general augmentation and amplification of normal bodily sensations. The operant theory predicts that pain behavior (operationalized as poorer endurance on the part of chronic low back pain patients as compared to the endurance of control subjects in a series of 6 working-to-tolerance treadmill tests) will decrease when no verbal or non-verbal feedback for treadmilling behavior is given. This hypothesis could not be confirmed in the present study. The hypochondriasis theory predicts that chronic pain patients will report more bodily sensations, both at rest and after treadmill exercises. This hypothesis was strongly supported by the findings of the present study.

Adult↗

An operant procedure to teach an echolalic, autistic child to answer questions appropriately.

An operant conditioning procedure to teach an autistic patient with rapid immediate echolalia to answer questions correctly was devised. The procedure involved positively reinforcing the patient immediately after a correct response and preventing incorrect responses. It is simple to implement and eliminates some of the structure and constraints inherent in previously described operant methods. This allows the procedure to be administered by a variety of therapeutic personnel and parents and in a variety of living situations.

Autistic Disorder↗

Behavioral effects of pre- and postnatal exposure to a mixture of low chlorinated PCBs in rats.

Polychlorinated biphenyl (PCB)-treated Wistar rats were tested on three different behavioral paradigms. Animals were pre- and postnatally exposed to a technical mixture of PCBs with a chlorine content of 42%. Exposure levels were 0, 5, or 30 mg/kg diet. These conditions did not affect the health of the dams, the litter size or weight, or the physical development of the offspring. Relative liver weights in the offspring, however, were elevated in a dose-dependent manner. Open-field ambulation, active avoidance learning, and operant conditioning on a fixed interval 30-sec schedule (FI-30-sec) were used to evaluate PCB-induced behavioral alterations. Ambulation was increased in 30-mg-treated rats at Day 22, but not at Day 120. There were more avoidance responses and intertrial responses in the 30-mg group than in both other groups. On the FI-30-sec schedule slightly more reactions were emitted by the 30-mg group during the first 10 sec of the interval than by the other animals. More pronounced, however, were the differences between groups in the temporal pattern of responses within the 30-sec interval. It is concluded that in rats PCB exposure causes consistent alterations in all of the tested activity-dependent behaviors.

Animals↗

Demonstration of lever pressing for oral ethanol by rats with no prior training or ethanol experience.

Male rats of the alcohol-preferring AA line were placed in an operant conditioning chamber with one lever delivering 10% alcohol solution and a second giving water. Free food and water were also continually available in the chamber so the animals should not have been motivated to obtain alcohol for reasons of hunger or thirst. The rats had never had alcohol previously. No shaping was used. The rats simply lived for the next 2 weeks in the operant chamber. All of them eventually learned to work for alcohol. Ethanol responding was significantly higher than pressing for water throughout the second week: on the last day, all rats pressed more than 300 times for alcohol and less than 40 times for water, took in a mean of 5.3 +/- 0.2 g/kg of ethanol, and obtained 72% of their total fluid as earned ethanol solution despite the presence of free water. Their acquisition was, however, much slower than that observed in male AA rats that had previously had prolonged access to drinking alcohol in their home cages. Living continually in the operant chamber is thought probably to have been an important factor in enabling the naïve rats to learn to work for alcohol.

Alcohol Drinking↗

Testosterone reinforcement: intravenous and intracerebroventricular self-administration in male rats and hamsters.

RATIONALE: Anabolic steroids are drugs of abuse. However, the potential for addiction remains unclear. Testosterone induces conditioned place preference in rats and oral self-administration in hamsters. OBJECTIVES: To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self-administration. METHODS: With each nose-poke in the active hole during daily 4-h tests in an operant conditioning chamber, gonad-intact adult rats and hamsters received 50 microg testosterone in an aqueous solution of beta-cyclodextrin via jugular cannula. The inactive nose-poke hole served as a control. Additional hamsters received vehicle infusions. RESULTS: Rats ( n=7) expressed a significant preference for the active nose-poke hole (10.0+/-2.8 responses/4 h) over the inactive hole (4.7+/-1.2 responses/4 h). Similarly, during 16 days of testosterone self-administration IV, hamsters ( n=9) averaged 11.7+/-2.9 responses/4 h and 6.3+/-1.1 responses/4 h in the active and inactive nose-poke holes, respectively. By contrast, vehicle controls ( n=8) failed to develop a preference for the active nose-poke hole (6.5+/-0.5 and 6.4+/-0.3 responses/4 h). Hamsters ( n=8) also self-administered 1 microg testosterone ICV (active hole:39.8+/-6.0 nose-pokes/4 h; inactive hole: 22.6+/-7.1 nose-pokes/4 h). When testosterone was replaced with vehicle, nose-poking in the active hole declined from 31.1+/-7.6 to 11.9+/-3.2 responses/4 h within 6 days. Likewise, reversing active and inactive holes increased nose-poking in the previously inactive hole from 9.1+/-1.9 to 25.6+/-5.4 responses/4 h. However, reducing the testosterone dose from 1 microg to 0.2 microg per 1 microl injection did not change nose-poking. CONCLUSIONS: Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.

Animals↗

Behavioral and hippocampal electrical changes during operant learning in cats and effects of stimulating two hypothalamic--hippocampal systems.

The electrical activity of the dorsal and ventral hippocampus and of the anterior and posterior neocortex is described and illustrated during the development of trained operant behavior in water-deprived cats learning to bar-press for water reward under three operant conditioning schedules: (a) continuous reinforcement; (b) alternating 10 sec periods of reinforcement and non-reinforcement; and (c) mixed reinforcement and non-reinforcement with special auditory and visual cues. In addition, the contrasting effects of 100 c/sec electrical stimulation of the medial and lateral hypothalamic systems upon hippocampal electrical activity and operantly trained behavior are reported. During the early stages of learning to bar-press for water reward, when close attention to the bar and water-well are required, hippocampal electrical activity manifests synchrony (theta rhythm) and neocortical electrical activity is desynchronized. Subsequently, as bar-pressing performance improves and requires little attention to the manipulanda, the pattern of hippocampal and neocortical electrical activity is one of irregular slow waves mixed with low voltage high frequency activity, characteristic of relative inattention and automatic performance. During alternating or mixed reinforcement and non-reinforcement schedules of operant training differential effects are observed during reinforcement and non-reinforcement periods, the latter being characterized generally by lower voltage, mixed low and high frequency activity, except when orienting and shifting of attention occurred with associated theta rhythm bursts. Stimulation of the medial hypothalamic system has a striking inhibitory effect upon bar-pressing for water reward. Bar-pressing ceases for many minutes but its eventually resumed at the pre-stimulation rate. In contrast, stimulation of the lateral hypothalamic system only interrupts bar-pressing for a matter of seconds. Possible causes of these differential effects, and especially the prolonged inhibition of bar-pressing induced by medial hypothalamic stimulation, are discussed.

Animals↗

Ambient light working times of visible light-cured restorative materials. Does the ISO standard reflect clinical reality?

OBJECTIVES: The aim of this study was to determine whether a custom built light box could reliably reproduce clinical conditions and whether the current ISO standard test for the working time of visible light cured (VLC) materials (ISO. Dental Resin-based Restorative Materials. ISO:4049, 1991) reflected clinical reality. METHOD: The ISO test requires a VLC material to remain homogenous after exposure to an 8 kLux light source for 60 s. The relationship between the intensity of ambient lighting and the working times of visible light-cured (VLC) restorative materials was investigated by exposing 23 different VLC composite resin materials to a range of light intensities and measuring the working time in seconds: (a) under clinical operating conditions; (b) in a custom light box at 24 kLux; and (c) at 8 kLux in the light box. Working times were determined by placing 0.06 g samples between two glass plates and gently rotating until clefts or voids appeared. RESULTS: Clinical lighting conditions (24 kLux) gave a mean working time of 54 s (s.d. 14 s). In the light box at 24 kLux the mean working time was 54 s (s.d. 11 s). At 8 kLux (under otherwise identical conditions) the mean working time was 162 s (s.d. 49 s). SIGNIFICANCE: A 24 kLux illuminance in the laboratory gives an optimal correspondence to operative lighting conditions. This is three times the lighting level required for ISO purposes, and gives more realistic working times.

Analysis of Variance↗

[A trouble in air conditioning in the operating area].

We experienced malfunction of air conditioning system in the operating area. Rust inside the circulating pipe to the operating area was an obstacle to inflow of cold and hot water. Installing an additional air conditioning system and treatment with chemicals to remove the dust made it possible to adjust room temperature appropriately. Anesthesiologists should be interested and understand equipments used in the operation area such as air conditioning system.

Air Conditioning↗

Conditioned whisking in the rat.

The rat's mystacial vibrissae are active during exploratory and discriminative behaviors, with individual vibrissae serving as elements in a receptive array scanned across object surfaces. To facilitate neurobehavioral analysis of this sensorimotor system, we have developed an experimental paradigm that confines vibrissa movements to a defined physical location, makes possible on-line monitoring of "whisking" activity, and brings such activity under associative control using operant conditioning procedures. Rats were secured, and movements of an identified bilaterally homologous pair of vibrissae (right and left gamma straddlers) were detected by laser-based photodetectors. Subjects were maintained on a water deprivation schedule, and whisker movements were monitored during adaptation to the test situation and after the clipping of other vibrissae on both sides of the snout. Rats were reinforced with water delivery for emitting vibrissa movements in the presence of a conditioned stimulus (tone) whose presentation was made contingent upon a prior period of nonwhisking. The rate and temporal distribution of vibrissa movements were brought under experimental control by means of interval and ratio reinforcement schedules. Although the procedures provide minimal information about the kinematics or topography of conditioned vibrissa movements, they permit the investigator to manipulate response parameters normally under the voluntary control of the animal in a preparation amenable to neurophysiological analysis.

Animals↗

Neuronal activity in the supplementary eye field during acquisition of conditional oculomotor associations.

1. The supplementary eye field (SEF) has been viewed as a premotor cortical field for the selection and control of saccadic eye movements. Drawing on studies of the neighboring premotor cortex, we hypothesized that if the SEF participates in the selection of action based on arbitrary stimulus-response associations, then task-related activity in the SEF should change during the learning of such associations. 2. Rhesus monkeys were operantly conditioned to make a saccadic eye movement to one of four targets (7 deg up, down, left, and right from center) in response to a foveal instruction stimulus (IS). One and only one of those four possible responses was arbitrarily designated "correct" for each IS. The monkeys responded to familiar ISs, four stimuli that remained unchanged throughout training and recording, as well as to novel ISs, which the monkeys had not previously seen. The monkeys initially chose responses to novel stimuli by trial and error, with near chance levels of performance, but quickly learned to select the correct saccade. 3. We studied 186 SEF cells as monkeys learned new visuomotor associations. Neuronal activity was quantified in four task periods: during the presentation of the IS, during an instructed delay period (i.e., after the removal of the IS but before a trigger or "go" stimulus), just before the saccade, and after the saccade during fixation of the target location. The discharge rate in each task period was considered a separate case for analysis, compared with that in a reference period preceding the IS, and eliminated from further analysis if not significantly different. 4. We observed two main categories of activity change during learning, which we termed learning selective and learning dependent. Learning-selective cases showed a significant evolution in activity as the monkeys learned which saccade was instructed by a novel IS, but had no significant modulation during trials with familiar ISs. Many of these cells were virtually inactive on trials with familiar ISs. However, they initially showed dramatic modulation when tested with a novel IS. As the monkey chose the correct saccade (or target) with increasing reliability, the modulation often decremented until the cell was again relatively unmodulated, as observed during familiar-IS trials. These cells usually remained relatively inactive until the monkeys were challenged to start learning another new stimulus-response association. Learning-selective activity was observed in all task periods, and 33 (18%) of the 186 adequately tested SEF cells showed learning-selective activity in one or more task periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of naloxone and naltrexone on self-injury: a double-blind, placebo-controlled analysis.

The effects of naloxone hydrochloride (Narcan) and naltrexone hydrochloride (Trexan) on the pervasive self-injury of a 12-year-old autistic and mentally retarded girl were examined. Using separate multiple schedule (A1/B/B') and withdrawal (A-B-A1B-A1) single-subject experimental designs, we investigated the effects of both opiate antagonists in serial fashion under double-blind, placebo-controlled conditions. Results of the two studies showed that self-injury increased during the naloxone trial, whereas a decrease to near zero rates of self-injury was observed following treatment with naltrexone. The differential effect produced by the two drugs was discussed in terms of drug half-life and the operant conditioning theory of extinction. Follow-up data showing near zero rates of self-injury for 22 months following the conclusion of active treatment with naltrexone indicated that the intervention produced a durable result.

Autistic Disorder↗

Minimized tolerance to the suppressive effects of CCK8 on operant responding.

This study was designed to determine if tolerance to cholecystokinin octapeptide (CCK8) could be prevented or minimized by spacing injections, and if an appetitive operant conditioning paradigm provides a sensitive baseline to test the effects of CCK8. Male Sprague-Dawley rats were trained to press a lever for water according to a fixed-interval 60-sec schedule of reinforcement. After response rate stabilized, rats were given a series of CCK8 (0.04 mg/kg, ip) injections spaced several days apart. The first injection of CCK8 produced complete response suppression during the 30-min test session, while later injections produced partial or complete suppression. Thus, tolerance to CCK8, as measured by operant response rate, may be minimized if injections are appropriately spaced.

Animals↗

Synthesizing animal and human behavior research via neural network learning theory.

Animal and human research have been "divorced" since approximately 1968. Several recent articles have tried to persuade behavior therapists of the merits of animal research. Three reasons are given concerning why disinterest in animal research is so widespread: (1) functional explanations are given for animals, and cognitive explanations are given for humans; (2) serial symbol manipulating models are used to explain human behavior; and (3) human learning was assumed, thereby removing it as something to be explained. Brain-inspired connectionist neural networks, collectively referred to as neural network learning theory (NNLT), are briefly described, and a spectrum of their accomplishments from simple conditioning through speech is outlined. Five benefits that behavior therapists can derive from NNLT are described. They include (a) enhanced professional identity derived from a comprehensive learning theory, (b) improved interdisciplinary collaboration both clinically and scientifically, (c) renewed perceived relevance of animal research, (d) access to plausible proximal causal mechanisms capable of explaining operant conditioning, and (e) an inherently developmental perspective.

Animals↗

Concerning the need for more sophisticated animal models in sensory behavioral toxicology.

It is necessary but not sufficient to develop laboratory animal models in sensory behavioral toxicology for screening toxic substances and for the analysis of sensory impairment at threshold levels of stimulation. It is important to develop more thorough and quantitative tests of impairment which in their greater complexity more accurately reflect the conditions and environmental demands of day-to-day life. Such greater complexity in stimulus conditions and behavior may also aid in monitoring not merely the state of the receptor organ but more central nervous processes which are the focus of assault by many known toxic substances. Techniques are described for studying such acoustic behaviors as intensity discrimination and frequency selectivity in guinea pig and monkey by use of operant conditioning procedures coupled with sensory testing (psychophysical) methods. Impaired auditory selectively and discrimination is shown to be correlated with histopathological changes in the inner ear. Slight modification of these procedures in animals may be used to investigate acoustically more intricate behaviors such as sound localization and the perception of frequency modulated acoustic signals as elements of speech and communication sounds.

Acoustic Stimulation↗