A temporal difference account of avoidance learning

A previously published study showed that stress may interfere with associative aversive learning and facilitate mood-related disorders. However, whether emotional stress alone affects aversive learning is unknown. Using three chamber-vicarious social defeat stress (3C-VSDS) model mice, we investigated the effect of emotional stress on aversive learning. An important origin of dopamine (DA) neurons, the zona incerta (ZI), is expected to be a novel target for the modulation of aversive learning. However, less is known about the circuit mechanism of ZIDA neurons in aversive learning. Here, we subjected mice to a fear-conditioning system (FCS) and observed an increased calcium activity of ZI TH+ neurons in aversive expectation during the conditioning phase, especially during the late stage of the conditional stimulus (CS) when CS and unconditional stimulus (US) pairings were used. Optogenetic inhibition of ZI TH+ neurons at the late stage of CS disrupted conditioned fear learning in mice. We further identified a TH+ projection from the ZI to the basomedial amygdala (BMA) and found that optogenetic inhibition of the ZI-BMA circuit could also block aversive learning. Finally, we used 3C-VSDS mice as a model of emotional stress. We found that the 3C-VSDS model mice demonstrated reduced aversive expectation associated with ZI TH+ neurons in the late stage of CS and impaired aversive learning in FCS. Optogenetic activation of ZI-BMA TH+ projections in the late stage of CS significantly reversed the aversive FCS learning disability of 3C-VSDS model mice. These data suggest that a TH+ circuit from the ZI to the BMA is required for aversive expectation, both at baseline and in 3C-VSDS-induced aversive learning deficits and that this circuit is a potential target for the modulation of aversive learning. Low activity of ZI-BMA TH+ projections is one reason for 3C-VSDS-induced aversive learning deficits.

Factors inflencing tolerance to the effects of Δ9-THC on a conditioned avoidance response

Psychologists make frequent use of nominal definitions indicating their agreement concerning the use of a particular verbal symbol. many cases such definitions, while operational, are purely arbitrary. Insofar as such definitions are convenient, contribute to conciseness of expression, or represent some unknowable, they are justified. They are not, however, to be preferred to symbols capable of analysis in terms of observable events. The original purpose of this paper was only to suggest a defining set of circumstances to characterize the onset of extinction trials in an avoidance conditioning situation. Using the proposed criterion for the onset of extinction trials in a re-analysis of previously obtained data revealed other information regarding the process of avoidance conditioning. These data will also be reported. Studies involving the acquisition and extinction of an avoidance response generally proceed somewhat as follows. An animal is placed into a twochamber apparatus having an electrifiable grid floor. After a period of adaptation, a conditioned stimulus (CS), such as a buzzer, is presented for a specified length of time. The unconditioned stimulus (UCS), electric shock, for example, follows the onset of the CS after another specified interval of time (the CSUCS interval). The experimental animal will, on initial trials, learn to escape shock by running or jumping over a barrier to the opposite end of the apparatus. With repeated presentations of the CS followed by the UCS the animal responds within the CS-UCS interval and thereby avoids shock entirely. Upon attaining some criterion of acquisition, such as 100% avoidance responses on a given number of successive days, extinction trials are initiated. This is accomplished by withholding the UCS regardless of the latencies of the animal's responses on all succeeding trials. Animals trained under avoidance conditions are usually highly resistant to extinction, and so-called extinction trials are, initially, at least, characterized by response latencies similar to those of avoidance responses occurring during acquisition trials. On the basis of the foregoing we see that, In the avoidance situation no objective change occurs between conditioning and extinction. This is in contrast to other types of conditioning in which the presence or absence of the UCS is immediately apparent (Murphy & Miller, 1956, p. 77). When to begin a series of extinction trials, it has been reasoned, must, then, remain arbitrary, that is, at E's discretion. It is, therefore, defined by the situation when E chooses to withhold the UCS. The above analysis is a fair representation of the implicit or explicit justification for the procedures involved in research studies on avoidance conditioning.

Movement disorders such as tremor and akinesia observed in Parkinson's disease have been attributed to dopamine (DA) depletion in the basal ganglia. The changes in subcortical neuronal discharge patterns that follow DA depletion have been a matter of much discussion. Here, we implanted rats with chronic recording electrodes bilaterally in the striatum (CPu) and external globus pallidus (GPe), and induced both acute and repeated DA blockade by administration of high-dose haloperidol. Recordings were made in baseline states, as well as before and after haloperidol injections, which rendered rats akinetic. The immediate physiological effect of pharmacological DA blockade was the development of prominent oscillatory firing in the 6-8 Hz range in both CPu and GPe. Importantly, this oscillatory pattern was not accompanied by consistent changes in the firing rate of either CPu or GPe neurons. Cross-correlation analysis further indicated that neurons within the CPu and GPe fired synchronously after DA blockade. Furthermore, although phase lags between neuronal discharges in the GPe and CPu were uniformly distributed prior to haloperidol administration, CPu significantly lagged GPe discharges after repeated DA blockade. Our results demonstrate that acute DA blockade is sufficient to produce synchronous oscillatory activity across basal ganglia neuron populations, and that prolonged DA blockade results in phase lag changes in pallidostriatal synchrony.

Cats, who had displayed escape or “fear”-like behavior by electrical stimulation of the midbrain central gray, were trained to interrupt the delivery of electrical stimulation of the midbrain central gray by plate pushing (switch-off behavior). After cats successfully learned to perform this switch-off behavior, they were further subjected avoidance conditioning trials in which neutral stimulus such as bell sound served as conditioned stimulus (CS), and electrical midbrain central gray stimulation as unconditioned stimulus (UCS). After cats reached the criterion of the avoidance learning, that is, appearance of the conditioned avoidance responses (CR) above 80%, then they were subjected extinction trials until they showed no CR. After that, they were given re-conditioning trials and extinction trials.Results are following : 1. Four cats out of seven succeeded in avoidance learning. Their stimulation sites were in the mid-paramedian position of the periaquedual gray matter (see Figs. 1 and 2).2. Two cats showed CR a little. One cat completely failed to show CR. Their stimulation points were in the basic and medial position of the midbrain central gray (see Figs. 1, 3, 4 and 5).These findings suggest differences between learning induced by intracranial stimulation and that induced by peripheral stimulation, and also differences between avoidance learning based on switch-off behavior induced by midbrain stimulation and that induced by hypothalamic stimulation.

Introduction. Theories of delusions often underplay the role of their content. With respect to persecutory delusions, taking threat as fundamental suggests that models of threat-related, aversive learning, such as the Conditioned Avoidance Response (CAR) task, might offer valid insights into the underlying normal and abnormal processes. In this study, we reappraise the psychological significance of the CAR model of antipsychotic drug action; and we relate this to contemporary psychological theories of paranoia. Methods. Review and synthesis of literature. Results. Anticipation and recall of aversive events are abnormally accentuated in paranoia. Safety (avoidance) behaviours may help perpetuate and fix persecutory ideas by preventing their disconfirmation. In addition, patients may explain negative events in a paranoid way instead of making negative self-attributions (i.e., in an attempt to maintain self-esteem). This defensive function only predominates in the overtly psychotic patients. The “safety behaviours” of paranoid patients, their avoidance of negative self-attributions, and the antiparanoid effect of antipsychotic medication all resonate with aspects of the CAR. Conclusions. The CAR appears to activate some normal psychological and biological processes that are pathologically activated in paranoid psychosis. Paranoid psychological defences may be a result of basic aversive learning mechanisms, which are accentuated during acute psychosis.

A motivational system approach to avoidance behavior is presented. According to this approach, a motivational state increases the probability of relevant response patterns and establishes the appropriate or “ideal” consummatory stimuli as positive reinforcers. In the case of feeding motivation, for example, hungry rats are likely to explore and gnaw, and to learn to persist in activities correlated with the reception of consummatory stimuli produced by ingestion of palatable substances. In the case of defense motivation, fearful rats are likely to flee or freeze, and to learn to persist in activities correlated with consummatory stimuli produced by flight from a dangerous place. Defense system activation is distinct from alarm reactions. The latter prepare the animal for probable noxious events, involve relatively intense negative affect and extinguish rapidly in situations where the noxious event no longer occurs. In contrast, defense system activation potentiates innate and modified defense reactions, thus preparing the animal for possible, but not necessarily probable, noxious events; it involves little or no negative affect and extinguishes very slowly when the noxious event no longer occurs. With these assumptions and the resulting model we attempt to resolve several long-standing problems in avoidance learning, including the low correlation between negative affect and avoidance performance, differential rates of extinction for avoidance performance and conditioned emotional responses, and evidence that some avoidance responses are much more easily learned than others. In addition, the model has implications for the study of parallels between appetitive and aversive motivation, sign tracking in aversive conditioning, and orientation of flight responses. Historical antecedents and alternative approaches are discussed.

Summary1. Two kinds of psychotropic drugs, chlorpromazine and imipramine, were examined in forty‐one dogs by means of the conditioned avoidance response and the electrocorticogram. These drugs were administered through three routes, namely intra‐peritoneal, intra‐arachnoid, and intra‐ventricular injection, with neither anaesthesia nor restraint.2. Following the intra‐arachnoid injection: Chlorpromazine produced the slow conditioned avoidance response in behavior, and asymmetrical ECoG, synchronized pattern. Imipramine demonstrated no attenuation of the conditioned avoidance response, and slight synchronization on the ECoG. The depressant action of chlorpromazine to the cerebral cortex was confirmed.3. Following the intra‐ventricular injection: Both drugs blocked tentatively the conditioned avoidance response and produced a continuous desynchronized pattern on the ECoG. The dissociation between the behavior and the ECoG was noticeable. The periventricular area might have a more important role on the conditioned avoidance response than the cerebral cortex.4. The difference of drug action between chlorpromazine and imipramine was manifested following the intra‐arachnoid injection.5. The significance of the function of the cerebral cortex and periventricular structures to the conditioned avoidance response and to the action of the drug was discussed.

5-Hydroxytryptamine 2C (5-HT2C ) receptor agonists have been suggested to possess an antipsychotic activity in several acute preclinical tests of antipsychotic drugs with low extra-pyramidal side effect liability. However, little is known about the long-term effect associated with chronic use of 5-HT2C receptor agonists. The present study examined whether repeated activation of 5-HT2C receptor with a highly selective 5-HT2C receptor agonist MK212 would induce a long-term change in its antipsychotic-like activity (either a sensitization or tolerance) in the conditioned avoidance response and MK801-induced hyperlocomotion tests. Sprague-Dawley rats were first tested under the intraperitoneal (i.p.) treatment of MK212 (0.25, 0.5, 1.0 mg/kg) for 5 consecutive days. Three days later, when all rats were injected with a low dose of MK 212 (0.25 mg/kg) and tested for avoidance responding, rats that had been pretreated with 1.0 and 0.5 mg/kg MK212 made significantly fewer avoidance responses than those that had been treated with vehicle (0.9% saline). However, this past drug exposure-induced group difference was not significant in the MK801-induced hyperlocomotion test. Overall, results from this study suggest that repeated treatment of MK212 is capable of inducing a dose-dependent sensitization of antipsychotic activity in conditioned avoidance response. The discrepancy in sensitization of MK212 in CAR and MK801-induce hyperlocomotion may be related to the different mechanism underlying the effect of MK212 in these two tests. © 2016 IUBMB Life, 68(12):985-993, 2016.

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: The logic of and a circuit for differentiating an avoidance response from an escape response are described. In avoidance conditioning experiments two procedures are commonly used to distinguis between avoidance and escape responses. However, under certain conditions these procedures are unreliable when electrical shock is used as the unconditioned stimulus. An electronic gate was developed which, in combination with an electronic timer, times the duration of shock w ich an animal actually receives. By noting the prescence or absence of shock, it is possible to differentiate an escape response from an avoidance response. Techniques to distinguish accurately an escape response from an avoidance response by an electronic gate and timer are presented. (Author)