Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal "bitter taste" cue

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral "taste" receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants-and concentrations of tastants-in the lumen of the gut can control ingestion.     

Incubation of conditional suppression is an associatively-based phenomenon

Ten rats were deprived of water and trained to lick a tube for saccharin reinforcement. In each of the two sessions that followed, the rats received six contiguous pairings of a 30-second illumination of the houselight and a 0.75 second, 0.10 mA electric shock while licking. No sign of conditioning was observed during the first experimental session, but profound conditioning was observed on the first and subsequent trials of the second conditioning session. No comparable change in the rate of licking was observed in groups of rats that received only presentations of the visual stimulus, only presentations of the electric shock, or random presentation of the visual stimulus and electric shock during the first conditioning session. These data establish that the incubation of conditional suppression is an associative phenomenon.     

Participation of feed-forward and feed-backward inhibition in the "priming" effect in hippocampal sections

Focal potentials (FP) elicited by stimulation of collateral-commissural fibers were recorded in the radial and pyramidal layers of the CA1 area in surviving mouse hippocampal slices. The influence of conditioning stimulation on responses in the tested neuronal pathway (the "priming" effect) at 50–1000 msec intervals between the conditioning and test stimuli and variable stimulation strengths was investigated. The relationship of the duration of the FP of the radial layer to the strength of the test stimulation at a 200 msec interval between the conditioning and test stimuli was studied in the first series of experiments. Three different regions of like relationship were distinguished. In region I (weak stimulation) the duration of the FP did not depend on the stimulus strength or on conditioning (i.e., the "priming" effect was not observed). In region II the duration of the FP in the control was shorter as compared with that observed in region I, which is associated with the triggering of the process of feed-forward inhibition. Conditioning led to the partial restoration of the duration of the FP (the "priming" effect, which evidently develops as the result of the suppression of feed-forward inhibition). In region III, by contrast with region II, the stimulation strength was sufficient for the suprathreshold excitation of the pyramidal neurons, which conditioned the development not only of feed-forward, but of feed-backward inhibition as well. The form of the FP in the radial layer is distorted in the process, and their duration cannot serve as an index of "priming." The influence of conditioning on the effect of paired-pulse depression of population peaks in the pyramidal layer was studied in the second series of experiments in order to identify possible changes in feed-backward inhibition. The principal effect consisted in a decrease in paired-pulse depression in the circuits tested; from this the conclusion was drawn of a suppression of feed-backward inhibition. It was concluded that both feed-forward and feed-backward inhibition are suppressed in "priming."Institute of the Brain, Russian Academy of Medical Sciences, Moscow. Translated from Neirofiziologiya, Vol. 24, No. 2, pp. 178–185, March–April, 1992.     

Inhibition of a conditioned reflex evoked emotional response as an "instrument" of avoidance

A method has been elaborated of training the human subjects to avoid electric shocks by overcoming the "fear" caused by a warning signal. A previously elaborated differentiated conditioned skin-galvanic response (SGR) to a sound stimulus served as a criterion of the emotional reaction. The SGR was projected on an oscilloscope screen. The electric shock was automatically delivered at the moment when the amplitude of the conditioned SGR exceeded the level marked on the screen. The subject was instructed, by overcoming the "fear", to retain the SGR amplitude below the level. If the subject succeeded in overcoming the conditioned SGR to the signal, the shock was not delivered. Since, the suppression of the conditioned SGR served as a "instrument" of avoidance and became consolidated as a habit based on a positive reinforcement. The subjects developed a stable attraction to repetition of training sessions in which they learned to suppress the "anxiety" caused by a signal of "threat".     

Prefrontal neurons coding suppression of specific saccades

The prefrontal cortex has been implicated in the suppression of unwanted behavior, based upon observations of humans and monkeys with prefrontal lesions. Despite this, there has been little direct neurophysiological evidence for a mechanism that suppresses specific behavior. In this study, we used an oculomotor delayed match/nonmatch-to-sample task in which monkeys had to remember a stimulus location either as a marker of where to look or as a marker of where not to look. We found a group of neurons in both the frontal eye field and the caudal prefrontal cortex that carried signals selective for the forbidden stimulus. The activity of these "don't look" neurons correlated with the monkeys' success or failure on the task. These results demonstrate a frontal signal that is related to the active suppression of one action while the subject performs another.     

Change in the signal properties of a conditioned stimulus during two-way avoidance conditioning in rats

Acquisition of two components of conditioned active avoidance behavior by rats was studied. First presentations of electroshock evoked a number of different behavioral reactions. However, after five trials many rats learned to escape punishment running away to another part of a shuttle-box. The efficiency of the avoidance reaction conditioning significantly depended on the ability of an animal to learn the correct escape reaction to the unconditioned stimulus. However, some animals were incapable for acquisition of the conditioned reaction despite their high level of successful escapes. Increase in the number of negative reactions to the conditioned stimulus (light) at the next stage of learning suggests that the conditioned stimulus becomes the signal of forthcoming punishment. The ability of an animal to identify the conditioned stimulus as a signal significantly affected the efficiency of conditioned avoidance acquisition.     

The effects of Mexidol on food conditioning and synaptic fine structure of hippocampal field CA1 in rats exposed to a single acoustic stimulation with ultrasonic components

The effect of exposure of rats to a complex acoustic signal with ultrasonic components on line structure of synapses of the CA1 field of the hippocampus was studied during a course treatment (two weeks) with broad-spectrum antioxidant Mexidol. Under the same conditions, the time course of food conditioning by a conditioned tone stimulus and acquisition of trace conditioned reflex (time interval counting) were studied in the same rat group. Rats non-exposed to stress against the background of Mexidol and without Mexidol treatment served as control. Analysis of fine structure of the vesicle redistribution in CA1 synapses revealed a reduction of the efficacy of synaptic transmission a day after the exposure to the complex acoustic stimulus. We found a negative effect of the complex acoustic stimulus on conditioning by tone and acquisition of time-counting trace reflex by rats. This effect was shown to be normalized by the course Mexidol treatment. The results suggests the expediency of Mexidol application for prevention of cognitive disorders, which are frequent under stress-inducing conditions.     

Development of passivity in the rat: effect of tranquilizers and antidepressants

Following the views on passivity as one of the features of depression-like behaviour in rats developing as a result of unavoidable painful stimulation an attempt was made to eliminate by antidepressant drugs the passivity manifested in an almost complete absence of motor searching reactions in an "open field" and a maze. However tranquilizing drugs rather than antidepressants to a greater extent induced the effect presupposed. Hence the type of passivity under study corresponds more likely to neurotized behaviour than to a special depression-like. In the second series of experiments the action was studied of multiple injections of antidepressants on similar manifestations of passivity as well as on alimentary instrumental conditioned responses in rats with initially expressed passive character of behaviour. In this case too neither the presupposed increase of motor searching reaction was observed nor any significant changes in the rate of instrumental conditioning nor elimination of its failures of a "refuse" type.     

Cardiovascular component of the context signal memory in the crab Chasmagnathus

Research on diverse models of memory in vertebrates demonstrates that behavioral, autonomic and endocrine responses occur together during fear conditioning. With invertebrates, no similar studies have been performed despite the extensive study of fear memory paradigms, as the context signal memory (CSM) of the crab Chasmagnathus granulatus, usually assessed by a behavioral parameter. Here, we study the crab’s CSM, considering both the behavioral response and the concomitant neuroautonomic adjustments resulting in a heart rate alteration. Results show that upon the first presentation of the visual danger stimulus, a heart arrest followed by bradycardia is triggered together with a conspicuous escape response. The latter declines throughout training, while heart arrests become sporadic and bradycardia tends to deepen along the session. At test, 24 h after training, the outcome clearly contrasts with that shown at training, namely, stimulus presentation in the same context induces lower escape, no heart arrests and quick suppression of bradycardia. These results support the view that the same memory process brings about the changes in both responses. High escape, heart arrest and bradycardia are considered three parameters of the unconditioned response while minor escape, no heart arrests and bradycardia attenuation are three parameters of the learned response.     

Pavlovian conditioning of shock-induced suppression of lymphocyte reactivity: acquisition, extinction, and preexposure effects

Recent research has indicated that physical stressors, such as electric shock, can suppress immune function in rats. The present study investigated whether a nonaversive stimulus that had been associated with electric shock would also impair immune function. Presentation of that conditioned stimulus (CS) by itself produced a pronounced suppression of lymphocyte proliferation in response to the nonspecific mitogens, Concanavalin-A (ConA) and Phytohemagglutinin (PHA). In further evidence of a conditioning effect, the suppression was attenuated by extinction and preexposure manipulations that degraded the associative value of the CS. These results indicate that a psychological or learned stressor can suppress immune reactivity independently of the direct effect of physically aversive stimulation or of ancillary changes in dietary and health-related habits.     

Probability analysis of elements of rat behavior after sudden and signalled interruption of food reinforcement

Probability analysis was carried out of the appearance of single elements of rats behaviour in the process of extinction of a conditioned alimentary motor reflex. The dynamics of effector behavioural components at a sudden cessation of reinforcement (usual schedule of extinction) was compared with cessation of reinforcement signalled by a previously differentiated signal and with reinforcement cessation preceded by a stimulus initially unknown to the animal. If the reinforcement cessation is signalled by a previously differentiated (negative) stimulus, in response to its action the animals "loose the aim", what is revealed in a rapid complete reduction of all elements of the goal-directed alimentary behaviour. Obviously differentiation signal actualises the memory trace of "nonreinforcement" which was formed in the previous negative experience of the animal; this is revealed in accelerated inhibition of the alimentary motor reflex under extinction.     

The effect of phenamine and caffeine on the ability to extrapolate in rats]

Solution of an extrapolation problem was studied on 28 albino rats (Way strain and laboratory population) and 68 hybrids (the first generation) of wild and laboratory rats in experiments with a screen--the search of food after the disappearance of the food stimulus from the animal's sight. Administration of caffeine (20 mg/kg) and d,l-amphetamine (0.1 mg/kg), though not changing the share of correct solutions, diminishes the number of "refusals" to solve it. Increased motor activity and diminished emotionality of the rats due to administration of the drugs, recorded in an open field test, are likely to cause a decrease in the number of refusals. Administration of d,l-amphetamine facilitates the process of conditioning which contributes to the greater number of positive solutions of the repeatedly presented task.     

Fear conditioning and shock intensity: the choice between minimizing the stress induced and reducing the number of animals used

Many fear conditioning studies use electric shock as the aversive stimulus. The intensity of shocks varies throughout the literature. In this study, shock intensities ranging from 0 to 1.5 mA were used, and the effects on the rats assessed by both behavioural and biochemical stress parameters. Results indicated a significant difference with respect to defaecation and freezing behaviour between controls and those animals that received a shock. Significant differences in corticosterone levels were also noted between controls and those groups that received a shock. No significant differences were found between the shock groups with regards to the stress parameters measured in our fear conditioning paradigm, indicating that the two shock groups were similarly stressed. Increased significance levels were noted for freezing behaviour as well as a lower standard error of means was found in the highest shock intensity group. We therefore recommend using the higher shock intensity (1.5 mA) as the rats in the higher shock intensity group were more homogeneously fear-conditioned and therefore the results should be more reproducible and robust than in the lower shock intensity group. This would allow for fewer rats to be used in order to gain an accurate impression of the conditioning paradigm employed.     

Changes in autonomic control of heart associated with classical appetitive conditioning in rats.

The aim of this study was to examine the changes in autonomic control of the heart associated with classical appetitive conditioning in rats. We trained rats to learn that a movement into a test chamber was followed by delivery of reward (contextual conditioning) and performed power spectral analysis of heart rate variability from electrocardiograms recorded using the telemetry system. We investigated the sympathovagal balance of autonomic regulation of the heart in response to not only the conditioned stimulus (the movement into the test chamber), but also the unconditioned stimulus (reward), and compared the results of these two kinds of emotional states; it might be considered that "the reward-expecting state" is evoked by the conditioned stimulus and "the reward-receiving state" is evoked by the unconditioned stimulus in rats. The reward-expecting state resulted in a significant increase in both low frequency (LF) power and high frequency (HF) power with no change in heart rate (HR) and LF/HF ratio, indicating that both sympathetic and parasympathetic activity increased with no change in sympathovagal balance. The reward-receiving state resulted in a significant increase in HR and a significant decrease in LF power, HF power, and LF/HF ratio, indicating that both sympathetic and parasympathetic activity decreased with predominance in the parasympathetic activity. These results suggest that the method performed in our present study might be useful for distinguishing between two different emotional states evoked by classical appetitive conditioning in rats.     

Development of ‘strategies’ utilized by albino rats in operant conditioning

A study concerning an operant conditioning of albino rats over a period of 6 months showed that different subjects progressively adopted a highly stable behaviour which could be called a ‘strategy’. Each one of these ‘strategies’ enables the subject to obtain, in a defined manner, a certain number of reinforcements within a given period; despite their different efficiencies, each one of these ‘strategies’ can be considered as ‘correct’. We have shown here that the duration of the conditioning session and the mean yield per stimulus depend on the choice of a given ‘strategy’.     

Contrasting the overexpectation and extinction effects

After many target stimulus (X)-unconditioned stimulus (US) pairings, further conditioning of X in the presence of another well-established signal for the US (A) disrupts X's behavioral control. Some researchers have argued that the mechanism underlying this so-called overexpectation effect is similar to that underlying extinction (a reduction in X's behavioral control due to X-alone presentations). Three conditioned suppression experiments with rats as subjects compared overexpectation and extinction. Experiment 1 replicated the basic overexpectation effect by showing that A disrupts responding to X more than does a previously neutral stimulus. Experiment 2 found that posttraining context exposure disrupts extinction but not overexpectation. Experiment 3 suggested that overexpectation and extinction are differentially sensitive to the effects of overtraining (compound reinforced or nonreinforced, respectively), such that extinction is enhanced by increases in the amount of nonreinforced trials and overexpectation is unaffected. These results are inconsistent with the view that overexpectation and extinction are driven by a common mechanism.     

Conditioning of active type avoidance in the rat : effect of the interval between conditioned stimulus and unconditioned stimulus

Lengthening the time interval between the conditioned stimulus and the unconditioned stimulus increases the number of active avoidance conditioned responses in subjects that have been trained to a stable level of performance in many previous conditioning sessions. In the present research, rats chosen from a population specially selected for low rates of avoidance conditioning have been used. In addition to this characteristic, subjects were chosen for the exhibition of an apparent absence of retention from one day to another. The dependency of the number of conditioned responses on the time interval between conditioned stimulus and unconditioned stimulus may lead to wrong evaluation of the subjects' conditioning level. In fact, the level of conditioning may be attributed to either learning or memory processes when in many cases it is determined only by the latency time of the conditioned response. The conditioned response has no possibility of manifesting itself when its latency time exceeds in length the time interval between conditioned stimulus and unconditioned stimulus.     

用条件性逃避反应建立简易的大鼠耳鸣检测方法

目的：用较简单的行为实验建立检测动物耳鸣的方法。方法：按照巴甫洛夫条件反射原理,参照Jastreboff的方法,建立“中断背景声音-大鼠逃跑”的条件反射;不再给电击,观察不同组别大鼠条件反射消退过程的行为表现,用公认的水杨酸耳鸣造模法来验证本方法的可靠性。结果：水杨酸组动物停止背景声音时不出现或较少出现逃跑反应,因为大鼠耳内仍有声音存在(耳鸣声),即条件刺激时有耳鸣的动物出现的逃跑反应次数小于无耳鸣的对照动物。结论：本实验设计可检测动物是否有耳鸣。     

The extinction context enables extinction performance after a change in context

One experiment with human participants determined the extent to which recovery of extinguished responding with a context switch was due to a failure to retrieve contextually controlled learning, or some other process such as participants learning that context changes signal reversals in the meaning of stimulus-outcome relationships. In a video game, participants learned to suppress mouse clicking in the presence of a stimulus that predicted an attack. Then, that stimulus underwent extinction in a different context (environment within the game). Following extinction, suppression was recovered and then extinguished again during testing in the conditioning context. In a final test, participants that were tested in the context where extinction first took place showed less of a recovery than those tested in a neutral context, but they showed a recovery of suppression nevertheless. A change in context tended to cause a change in the meaning of the stimulus, leading to recovery in both the neutral and extinction contexts. The extinction context attenuated that recovery, perhaps by enabling retrieval of the learning that took place in extinction. Recovery outside an extinction context is due to a failure of the context to enable the learning acquired during extinction, but only in part.