US-preexposure Effect Research Articles

Contextual control of the retardation of flavour aversion learning by preexposure to the unconditioned stimulus: Acquisition or retrieval deficit?

Two experiments, using rats as the subjects, and flavour aversion learning with an injection of lithium chloride (LiCl) as the unconditioned stimulus (US), examined the effects of a context shift between phases of the procedure on the retardation of learning produced by preexposure to the US. Experiment 1 showed that the US-preexposure effect (the reduction in the size of the conditioned aversion) was not attenuated when the animals were given both preexposure to the US and the conditioning procedure in a novel context but received the test phase in a different context (the home cages). Experiment 2 showed that, after degrading the injection cues–illness association by interpolating saline injections between LiCl preexposures, the US-preexposure effect was attenuated when there was a context shift between preexposure and conditioning, but that the context shift was without effect when it occurred between conditioning and test. These results are consistent with the proposal that US preexposure obtained in this procedure has its effect by interfering with the formation of the target association; they provide no support for the suggestion that the effect depends on interference at the test stage.

Effect of pretrial running on running-based taste aversion learning in rats.

Voluntary wheel running works as an effective unconditioned stimulus (US) to establish conditioned taste aversion (CTA) in rats with a preceding taste solution as a conditioned stimulus (CS): repeated CS-US pairings evoke avoidance of the CS in the two-choice (CS vs. tap water) test administered at the end of the training. Experiment 1 demonstrated that exposure to running immediately before each CS-US trial alleviates CTA. Subsequent two experiments explored the characteristics of the proximal US-preexposure effect: the alleviation of CTA by the pretrial running was not affected by changing the background contexts between the pretrial and the trial running (Experiment 2) or by signaling the pretrial running via another taste cue (Experiment 3). These results indicate the robustness of the proximal US-preexposure effect and fit well with the predictions of Wagner's (1976, 1978) priming theory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Flavor Aversion Learning Based on Running: A Review

Wheel running establishes aversion in rats to a flavored solution consumed shortly before the running. Many studies have shown that this is a case of Pavlovian conditioning, in which the flavor and running respectively act as the conditioned stimulus (CS) and the unconditioned stimulus (US). The present article introduces some procedural variables of this running-based flavor aversion learning (FAL), including subjects, CS agents, US agents, and drive operations. This article also summarize various behavioral features of Pavlovian conditioning demonstrated in running-based FAL including the law of contiguity despite long-delay learning, extinction and spontaneous recovery, CS-preexposure effect, remote and proximal US-preexposure effects, degraded contingency effect, inhibitory learning by backward conditioning, stimulus overshadowing, associative blocking, and higher-order contextual control. Also reviewed are several hypotheses proposed for the underlying psychophysiological causes of running-based FAL (activation of mesolimbic dopamine system, gastrointestinal discomfort, motion sickness, energy expenditure, general stress, and anticipatory contrast). At the end of the article, we visit the question of most general interest about running-based FAL: why pleasurable activity of voluntary running yields aversive learning in rats.

Unconditioned Stimulus Pre-exposure Interferes with Conditioned Taste Aversion in Rats

Pairing of a gustatory CS and the visceral US induced by lithium chloride (LiCl) results in reduction of consumption of CS solution. This reduction is termed conditioned taste aversion (CTA). Pre-exposure to CS alone prior to the conditioning disrupts the conditioning (latent inhibition) and so is pre-exposure to US. The US pre-exposure effect is hypothesized to be due to tolerance, habituation, or the associative blocking effect. We studied the dose effect of US pre-exposure on CTA. In 3 experiments, rats were exposed to 10 doses of LiCl before the CTA procedure that consisted of ingesting a saccharin solution (0.1%) followed by injection of a constant dose of LiCl (7.632mg/rat). If the pre-exposure reduced the associability of the US, the CTA should be less. Exp. 1: Pre-exposure to 4 or 8 ml/kg of 0.15M LiCl, 1, 2 or 4 days prior to CTA did not have effect. Exp. 2: Pre-exposure to 0.5, 1, 2, 16, 32 ml/kg 1-day prior disrupted CTA. Exp. 3: Pre-exposure to 1, 16, 20, 32, 40 ml/kg 2-days prior disrupted CTA. Summary: (a) The pre-exposure effect was the same whether the pre-exposure occurred 1 or 2 days prior to conditioning. (b) A clear dose-effect relationship existed. (c) The relation was not monotonic. (d) The lowest preexposure dose, 0.5ml/kg of 0.15M LiCl, not strong enough to induce CTA by itself, was effective. (e) Upon repeated pairing of CS and US, CTA became more pronounced. The results do not support the hypotheses mentioned earlier.

US-preexposure effects in flavor-preference and flavor-aversion learning with nonnutritive USs

In two experiments, rats received exposure to either a saccharin or quinine solution followed by conditioning with a solution of almond as the conditioned stimulus (CS) and either saccharin or quinine as the unconditioned stimulus (US). In Experiment 1, rats received preexposure and conditioning using saccharin as the US; in Experiment 2 quinine was the US. In both cases the magnitude of the conditioning effect (an enhanced preference for the CS in Experiment 1; a reduced preference in Experiment 2) was reduced by preexposure to the US. The results provided confirmation of the occurrence of the US-preexposure effect in the flavor-preference procedure and demonstrate that the effect can be obtained with nonnutritive USs that lack significant post-oral consequences. The implications of these results for theories of the US-preexposure effect are discussed.

The unconditioned stimulus pre‐exposure effect in preweanling rats in taste aversion learning: Role of the training context and injection cues

The unconditioned stimulus pre-exposure effect (US-PE) refers to the interference paradigm in which acquisition of the conditioned response is retarded due to prior experience with the US. Most studies analyzing the psychological mechanisms underlying this effect have been conducted with adult rats. The most widely accepted hypothesis explains this effect as a contextual blocking effect. Contextual cues associated with the US block the conditioned stimulus (CS)-US association during conditioning. The modulatory role of a context devoid of distinctive olfactory attributes is not observable until approximately PD23 in rats, including modulation of interference paradigms such as latent inhibition or extinction. In this study, we analyzed US-PE in preweanling rats along with the role of the training context in this effect in terms of conditioned taste aversion preparation. Pre-exposure to LiCl before conditioning retarded the acquisition of taste aversion. The US-PE was observed in preweanling rats when, during pre-exposure, subjects were exposed to the conditioning context, and this effect was not attenuated either by the administration of the US in a familiar environment (Experiment 1a), or by the presence of an alternative, more salient context during pre-exposure (Experiment 1b). Additionally, the US-PE was still observed when the route by which the US was administered was changed between the pre-exposure and conditioning phases (Experiment 2a) as well as when the injection cues were removed during conditioning (Experiment 2b). These experiments show a strong US-PE in preweanling rats and fail to support the contextual blocking hypothesis, at least in this stage of ontogeny.

Signaling the unconditioned stimulus during the preexposure phase does not attenuate the unconditioned stimulus preexposure effect in preweanling rats

The unconditioned stimulus preexposure effect (US-PE) is defined as an attenuation of the conditioned response after preexposure to the US prior to conditioning. Evidence exists that this effect can be weakened or eliminated by the presence of a signal predicting the US during the preexposure phase. This evidence has been found consistently across a variety of procedures in adult rats. The aim of the present study was to evaluate whether, in infant rats, signaling the US (LiCl) during preexposure with a salient cue (almond odor) attenuates the US-PE. During the preexposure phase, preweanling rats received three (Experiment 1) or one (Experiment 2) preexposures to LiCl, preceded by exposure to almond odor. Appropriate control groups were also included in these experiments. After preexposure, two conditioning trials were carried out in which subjects were given LiCl after saccharin consumption. During preexposure, three (Experiment 1a), although not one (Experiment 2a), contingent exposures to almond odor and LiCl resulted in a strong odor aversion. Extinction of the learned taste aversion was facilitated by prior experience with LiCl (Experiments 1b and 2b). This effect was observed regardless of whether or not LiCl was signaled by the almond odor. These results do not coincide with the associative hypotheses proposed to explain the US-PE, nor are they concurrent with alternative explanations based on the learned helplessness phenomenon.

Analysis of the US-preexposure effect in flavor acceptance conditioning

In three experiments, rats received exposure to a sucrose solution followed by conditioning with a neutral flavor as the conditioned stimulus (CS) and sucrose as the unconditioned stimulus (US). In Experiments 1 and 2, some rats were given both the preexposure and the conditioning phases in a highly familiar context (the homecage), whereas other animals received both phases in a novel and distinctive context. In both cases the magnitude of the conditioning effect was reduced by preexposure to the US. Experiment 3 directly assessed the possible role of contextual cues by changing the context between the exposure phase and the conditioning phase but found no loss of the US-preexposure effect in these conditions. These results lend no support to the blocking-by-context account of the US-preexposure effect; alternative interpretations are considered.

Analysis of us-preexposure effects in appetitive conditioning.

In two experiments, rats received preexposure to one type of food followed by autoshaping in which presentation of one lever was associated with the preexposed food, and presentation of another lever with a novel type of food pellet. In both it was found that acquisition of the leverpress response occurred more readily on the lever associated with the novel food. This example of the US (unconditioned stimulus) preexposure effect is not to be explained in terms of the development of competing responses during preexposure. Explanations in terms of blocking by contextual cues and of habituation to the US are considered.

Reinforced stimulus preexposure effects as a function of US intensity: Implications for understanding the Hall–Pearce effect

Three conditioned suppression experiments examined the Hall–Pearce (1979) negative transfer effect in rats. Experiment 1 replicated the effect: CS-US weak pairings retarded subsequent fear conditioning to the CS as a result of CS-US strong pairings. The size of this retardation was less than that produced by non-reinforced CS presentations (latent inhibition). When the magnitude of the US weak was reduced in Experiment 2, the Hall–Pearce effect was greater than latent inhibition. Experiment 3 confirmed the findings of the two previous experiments, and demonstrated that magnitude of the Hall–Pearce negative transfer effect is inversely related to the magnitude of the US weak. From these findings it is suggested that the Hall–Pearce effect consists of a balance between a positive transfer of associative strength, and negative transfer based on CS- and US-preexposure effects.

ERROR-PROCESSING DEFICITS IN CHILDREN AGED 9-12 YEARS WHO PRESENT PSYCHOTIC-LIKE EXPERIENCES AND OTHER ANTECEDENTS OF SCHIZOPHRENIA

Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic–polyribocytidilic acid (Poly(I:C)) at a dose of 5 mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-α was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.

Interactions between retroactive-interference and context-mediated treatments that impair Pavlovian conditioned responding

In Pavlovian fear conditioning, context-mediated decrements in conditioned responding (e.g., the US preexposure effect) can counteract competition between cues trained together (e.g., overshadowing). Two experiments were conducted using rats in a conditioned lick suppression preparation to determine whether context-mediated competition also counteracts competition between c ues trained separately (retroactive interference, or RI). In Experiment 1, a combination of degraded contingency and RI treatments produced less of a decrement in conditioned responding than did either of those treatments alone. Experiment 2 showed that RI treatment attenuates the normally deleterious effect of trial massing. The results suggest that empirical similarities are shared by interference between cues trained apart and competition between cues trained together.

Disruption of the US pre-exposure effect and latent inhibition in two-way active avoidance by systemic amphetamine in C57BL/6 mice

Pre-exposure to either one of the two to-be-associated stimuli alone is known to reduce the efficiency of the learning of their association when they are subsequently paired explicitly. In classical conditioning, pre-exposure to the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre-exposure to the unconditioned stimulus (US) results in the US pre-exposure effect (USPEE). Considerable evidence supports an important role of central dopamine in the regulation and modulation of LI; it has been suggested that the USPEE may be similarly controlled by dopamine, but this parallelism has only been directly demonstrated in the conditioned taste aversion paradigm. The present study tested this hypothesis by comparing the efficacy of systemic amphetamine treatment to affect the expression of LI and the USPEE in a two-way active avoidance paradigm. C57BL/6 male mice were tested in active avoidance using a tone CS and a foot-shock US. Twenty-four hours before, they were pre-exposed to 100 presentations of the CS or the US, or to the test apparatus only. Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure and conditioned avoidance test, in which the mice learned to avoid the shock by shuttling in response to the tone. Amphetamine disrupted both stimulus pre-exposure effects, thus, lending further support to the hypothesis that the USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence, the USPEE paradigm may represent a valuable addition to the study of dopamine-sensitive processes of selective learning currently implicated in LI and Kamin blocking.

Appetitive sensitization by amphetamine does not reduce its ability to produce conditioned taste aversion to saccharin

Previous exposure to amphetamine attenuates its ability to induce conditioned taste aversion (CTA). Because amphetamine, unlike emetic agents like LiCl, possesses appetitive properties that sensitize when it is administered repeatedly, the present study assessed the contribution of sensitization to this US-pre-exposure effect (US-PEE). It was found that not all sensitizing regimens of systemic amphetamine injections produce a US-PEE. In addition, previous exposure to amphetamine in the VTA, where it acts to induce sensitization but not CTA, did not produce a US-PEE. It is concluded that amphetamine sensitization alone does not modulate this drug's ability to produce CTA. Implications of these findings for anatomically based associative and non-associative models of CTA and the US-PEE are discussed.

Familiarization and cross-familiarization of wheel running and LiCl in conditioned taste aversion

Familiarization with an unconditioned stimulus (US) interferes with the learning of subsequent Pavlovian conditioned associations. We conducted a series of experiments exploiting this US preexposure effect to elucidate the underlying mechanism of conditioned taste aversion in rats induced by voluntary wheel running. Experiment 1 demonstrated that running-induced taste aversion was alleviated if rats had sufficient experience of running in advance. In Experiments 2A and 2B, preexposure to wheel running had no effect on subsequent taste aversion conditioning by lithium chloride (LiCl) injection. In Experiment 3, however, we observed a weak partial interference from the LiCl injection pretreatment to the subsequent conditioning by wheel running US. This US crossover effect suggests the possibility that wheel running and LiCl injection share a common or similar physiological mechanism in inducing taste aversion.

Immunological stress at the maternal–foetal interface: A link between neurodevelopment and adult psychopathology

Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic–polyribocytidilic acid (Poly(I:C)) at a dose of 5 mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-α was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.

The role of habituation of the response to LiCl in the US-preexposure effect

In two experiments, rats received preexposure consisting of six intraperitoneal injections of lithium chloride (LiCl). This treatment reduced the magnitude of the unconditioned response (UR; suppressed consumption of a novel flavor) evoked by an additional injection (Experiment 1) or by oral consumption (Experiment 2) of LiCl. In both experiments, preexposure also attenuated the acquisition of a conditioned aversion with an LiCl injection as the unconditioned stimulus (US) but had no effect on the aversion produced when the US was oral consumption of LiCl (Experiment 2). These results are consistent with the view that the reduced ability of the preexposed US to serve as a reinforcer depends on blocking by injection-related cues and is independent of habituation of the UR recorded in the present study. Possible interpretations of this dissociation are discussed.

The US-preexposure effect in lithium-induced flavor-aversion conditioning is a consequence of blocking by injection cues.

In 2 experiments, rats received flavor-aversion conditioning in which the unconditioned stimulus (US) was an orally consumed solution of lithium chloride (LiCl). The resulting aversion was not attenuated by giving preexposure to injections of LiCl, although such preexposure did attenuate aversions established using injected LiCl as the US (Experiment 1). This outcome suggests that blocking by injection-related cues is responsible for the US-preexposure effect observed in this situation. Experiment 2 confirmed this interpretation by showing that presenting such cues (by giving an injection of saline) at the time that the LiCl was drunk resulted in an attenuation of conditioning in animals preexposed to injections of LiCl. The US-preexposure effect obtained in these experiments can be explained solely in terms of blocking by injection cues, although other mechanisms may contribute to the effect seen in other flavor-aversion paradigms.

Nicotine-conditioned locomotor sensitization in rats: assessment of the US-preexposure effect

In rats, stimulus–nicotine associations can be altered by preexposure to the nicotine US (unconditioned stimulus). This alteration differs with the conditioning preparation. In a conditioned taste avoidance preparation, preexposure to nicotine weakens conditioning. In contrast, nicotine preexposure enhances acquisition of a nicotine-conditioned place preference. No one has examined the effects of US preexposure on nicotine locomotor conditioning. In three separate experiments, we assessed the effects of nicotine preexposure on the subsequent expression of conditioned hyperactivity produced by a nicotine US. We found evidence for nicotine-conditioned locomotor sensitization in non-preexposed rats that received repeated pairings of a distinct context with the psychomotor effects of a 0.42mg/kg dose of nicotine (free base). Conditioning was not observed at lower nicotine doses (0.18 and 0.11mg/kg) in non-preexposed rats. Preexposure to the 0.42 and 0.18mg/kg doses of nicotine (3 or 9 days) attenuated acute locomotor suppression and enhanced the development of locomotor sensitization to that same dose. Despite similar qualitative shifts in the locomotor profile induced by preexposure to the nicotine US, conditioned hyperactivity was only altered after 3 or 9 days of preexposure at the 0.18mg/kg dose. Thus, similar to place conditioning, nicotine preexposure can enhance the subsequent effectiveness of the nicotine US in a locomotor conditioning preparation.

Repeated administration of LiCl produces an unconditioned stimulus preexposure effect in backward excitatory CTA but not habituation of the unconditioned increment in neophobia

In one experiment using conditioned taste aversion and the unconditioned stimulus (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days, whereas two other groups received saline. Following this phase, all groups were given a novel flavour (saccharine) to drink following either LiCl (group preexposed and one of the control groups) or saline injections (the remaining control group) and the consumption of the flavour was assessed. After this neophobia test, the acquired saccharine aversion was evaluated. The results show that three LiCl injections are enough to produce a US preexposure effect on backward excitatory taste aversion conditioning, whereas this number of injections procedure does not produce habituation of the increment in neophobia, an unconditioned response to the LiCl. The results are discussed taking into account different mechanisms involved in US preexposure effect.