Unconditioned Stimulus Preexposure 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.

Examinations of CS and US preexposure and postexposure in conditioned taste aversion: Applications in behavioral interventions for chemotherapy anticipatory nausea and vomiting

Examining CS or US preexposure and postexposure to dissociate conditioned stimulus (CS)-unconditioned stimulus (US) conditioned learning and apply these findings to alleviate anticipatory nausea and vomiting are crucial for cancer chemotherapy patients. The present study utilized a conditioned taste aversion (CTA) paradigm in rats to develop a new behavioral intervention. Experiment 1 evaluated Control, Conditioning, CS preexposure, and CS postexposure groups. Experiment 2 evaluated Control, Conditioning, US preexposure, and US postexposure groups. After conditioning in both experiments, rats were given the CS alone without the US once per day over three trials, and their conditioned taste aversion was measured. The results showed that both CS preexposure and US preexposure interfered with subsequent CS-US conditioning, indicating that both induced proactive interference. Although CS postexposure interfered with prior CS-US conditioning, which indicated extinction, US postexposure did not alter CS-US conditioning. The findings should be considered for the development of new nonpharmacological clinical interventions for cancer patients with chemotherapy-induced anticipatory nausea and vomiting.

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 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.

Analysis of the learned irrelevance effect in appetitive pavlovian conditioning.

In Experiments 1 and 2 rats received uncorrelated presentations of a light conditioned stimulus (CS) and a food unconditioned stimulus (US) on each day of a preexposure phase. Control subjects received the same number of USs during the first half of preexposure and the same number of CSs during the second. Uncorrelated preexposure retarded inhibitory conditioning. Experiment 3 showed, however, that the different patterns of US preexposure experienced by the two groups could in itself influence the course of subsequent inhibitory conditioning. When this factor was equated by restricting the uncorrelated treatment to the first half of the pre-exposure phase (Experiment 2) or by extending the control treatment throughout the phase (Experiment 4) it was found that uncorrelated preexposure retarded excitatory conditioning, but facilitated inhibitory conditioning. This outcome challenges an interpretation in terms of the concept of learned irrelevance, which predicts that uncorrelated preexposure should retard both forms of conditioning.

Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response is sensitive to context

Conditioning-specific reflex modification occurs when an unconditioned response is modified in the absence of the conditioned stimulus as a result of pairings of the conditioned stimulus and an unconditioned stimulus. In two experiments, we assessed conditioning-specific reflex modification in either a novel context (Experiment 1) or a context different from, but equally familiar in relation to, the training context (Experiment 2). Conditioning-specific reflex modification did not demonstrate sensitivity to a novel context but did demonstrate sensitivity to a change in familiar context. The data cannot be explained by unconditioned stimulus preexposure, overtraining, or context insensitivity. The results suggest that conditioning-specific reflex modification models normal stress and may be used to evaluate theories of and treatments for posttraumatic stress disorder.

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.

Decremental effects of context exposure following delay eyeblink conditioning in rabbits.

The conditioning context arises from the relatively static features of the training environment. In rabbit eyeblink conditioning, procedures that retard acquisition (conditioned stimulus [CS] preexposure, unconditioned stimulus preexposure, blocking manipulations) are attenuated by context changes. In this article the authors investigate the effect of context exposure after initial delay conditioning. After conditioned responses (CRs) were established, one group received 6 sessions of context exposure, whereas control groups either remained in their home cages or received exposure to handling and a novel context. Thereafter, all groups received CS-alone testing. The expression of CRs was substantially reduced following context exposure relative to any retention loss in the home-cage control. Exposure to handling and a novel context facilitated the CRs rather than reducing them.

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.

Essential Neuronal Pathways for Reflex and Conditioned Response Initiation in an Intracerebellar Stimulation Paradigm and the Impact of Unconditioned Stimulus Preexposure on Learning Rate

It has been demonstrated previously that pairing of tone CS and intracerebellar stimulation of lobule HVI white matter as the US produces conditioning that is robust and in many ways similar to that obtained with an airpuff US. The first study in this report addressed the effect of interpositus lesions on conditioned performance in rabbits trained with white matter stimulation as the US. It was found that interpositus lesions effectively eliminated the CR irrespective of the behavioral response measured. In addition, it was shown that the interpositus lesions also abolished the UR, providing strong evidence that the effects of the electrical stimulation were confined to the cerebellum and did not require the activation of brainstem structures. The second experiment examined performance on US-alone trials of varying durations. Response initiation within 100 ms of the US onset, regardless of US duration, indicated that reflex generation could not be due to rebound excitation of the interpositus following termination of Purkinje cell inhibition of that structure but instead likely reflects orthodromic activation of interpositus neurons via climbing fiber and/or mossy fiber collaterals. The impact of US preexposure on associative conditioning in this paradigm was also determined. Animals which received only 108 US-alone trials were massively impaired during subsequent training compared to rabbits that received fewer than 12 US-alone trials.

Relationship between Fos Production and Classical Fear Conditioning: Effects of Novelty, Latent Inhibition, and Unconditioned Stimulus Preexposure

The relationship between FOS production in the sensory cortex and limbic system and the ability of C57BL/6N mice to acquire context- and tone-dependent freezing were investigated after fear conditioning, which was achieved by exposure of mice to context only or context and tone (10 kHz, 75 dB) as conditioned stimuli (Cs) paired with an electric footshock (0.7 mA, constant) as unconditioned stimulus (Us). The effect of preexposure to Cs or Cs paired with Us on FOS production and learning was also tested. It was demonstrated that high simultaneous FOS production in the parietal cortex, hippocampus, and amygdala paralleled the ability of mice to acquire strong freezing responses to novel Cs. After contextual preexposure (latent inhibition), FOS production could be elicited in the central amygdala only by shock and in the basolateral amygdala only by tone. Under these conditions, the ability of mice to acquire contextual freezing was almost abolished, whereas tone-dependent freezing was reduced. Lacking FOS production in the central amygdala after preexposure to context followed by shock (Us preexposure effect) paralleled the inability of mice to acquire tone-dependent freezing, although the tone elicited FOS production in the basolateral amygdala. On the basis of these findings it was concluded that synchronous Cs- and Us-induced FOS production in several defined forebrain areas was accompanied with associative learning of novel stimuli, and that a subsequent low level of FOS production might have been responsible or indicative for delayed conditioning to those stimuli.

Comparator mechanisms and conditioned inhibition: Conditioned stimulus preexposure disrupts Pavlovian conditioned inhibition but not explicitly unpaired inhibition.

Three conditioned lick-suppression experiments with rats examined the effects of pretraining exposure to the conditioned stimulus (CS) on behavior indicative of conditioned inhibition. After CS-preexposure treatment, subjects received either Pavlovian conditioned inhibition training or explicitly unpaired inhibition training with the preexposed CS. The inhibitory status of the CS was then assessed with a retardation (Experiment 1) or a summation (Experiment 2) test. Experiment 3 controlled for the unconditioned stimulus-preexposure effect being a potential confound in Experiments 1 and 2. As predicted by the comparator hypothesis (R. R. Miller & L. D. Matzel, 1988), the CS-context association that developed during the CS-preexposure phase disrupted the expression of Pavlovian conditioned inhibition but not the expression of explicitly unpaired inhibition.

Comparator mechanisms and conditioned inhibition: Conditioned stimulus preexposure disrupts Pavlovian conditioned inhibition but not explicitly unpaired inhibition.

Three conditioned lick-suppression experiments with rats examined the effects of pretraining exposure to the conditioned stimulus (CS) on behavior indicative of conditioned inhibition. After CS-preexposure treatment, subjects received either Pavlovian conditioned inhibition training or explicitly unpaired inhibition training with the preexposed CS. The inhibitory status of the CS was then assessed with a retardation (Experiment 1) or a summation (Experiment 2) test. Experiment 3 controlled for the unconditioned stimulus-preexposure effect being a potential confound in Experiments 1 and 2. As predicted by the comparator hypothesis (R. R. Miller & L. D. Matzel, 1988), the CS-context association that developed during the CS-preexposure phase disrupted the expression of Pavlovian conditioned inhibition but not the expression of explicitly unpaired inhibition.

Effects of US-Alone Presentations on Human Evaluative Conditioning

In the context of evaluative conditioning, the effects of additional presentations of the unconditioned stimulus (US) prior to conditioning (US preexposure) or after conditioning (US postexposure) were examined using between- and within-subjects control conditions. Two experiments that differed with respect to the nationality of the subjects were conducted. In both experiments, US-alone presentations reduced the magnitude of the evaluative response. The US pre- and postexposure effects were observed in subjects classified as aware as well as in subjects classified as unaware of the experimental contingencies. Another finding is that the evaluative conditioning procedure described by Martin and Levey (1978; Levey & Martin, 1975) resulted in reliable conditioning effects also in an American sample, thus extending the scope of that special evaluative conditioning paradigm. The findings are discussed in the context of recent models of classical and evaluative conditioning. Especially, the unexpected US postexposure effect gives rise to speculations concerning the learning process underlying evaluative conditioning.

Effects of a Retention Interval on the US-Preexposure Phenomenon in Flavor Aversion Learning

Two experiments, using rats as subjects, examined the effects of a retention interval on the retardation of flavor aversion learning produced by prior exposure to the unconditioned stimulus (US). Experiment 1 showed that the US-preexposure effect was attenuated when a 15-day retention interval was interposed between preexposure and conditioning, but that the same interval was without effect when it occurred between conditioning and testing. Experiment 2 confirmed these findings and also demonstrated that these retention intervals did not influence the conditioned aversion shown by control subjects not given US preexposure. These results are consistent with the proposal that the US preexposure 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.

Remote and Proximal US Preexposure and Aging Effects in Taste Aversion Learning in Rats

Misanin, J. R., T. D. Hoefel, C. A. Riedy and C. F. Hinderliter. Remote and proximal US preexposure and aging effects in taste aversion learning in rats. Physiol Behav 61(2) 221–224, 1997.—Age as a factor in the effect of proximal and remote unconditioned stimulus (US) preexposure on conditioned taste aversion in weanling, young adult, and old rats was studied in 2 experiments. In Experiment 1, 6 daily US preconditioning exposures attenuated conditioning in weanlings and young adults, but not in old rats. In Experiment 2, exposure to a single US 1 h before the conditioning trial curtailed conditioning at all age levels. These results are explained in terms of age differences in familiarity with the conditioning context and Wagner's information-processing model for self- and retrieval-generated disruption of conditioning.

The Importance of Context in the US Preexposure Effect in CTA: Novel versus Latently Inhibited Contextual Stimuli

Three experiments were conducted to examine the role of novel contextual stimuli in producing the unconditioned stimulus (US) preexposure effect. Experiment 1 demonstrated that novel contextual stimuli produce a significantly stronger US preexposure effect than familiar or “latently inhibited” contextual stimuli. Moreover, subjects preexposed in the presence of latently inhibited contextual cues failed to show a significant US preexposure effect. Experiments 2 and 3 attempted to provide evidence that the addition of a single novel stimulus to the latently inhibited context would result in a significantly stronger US preexposure effect than when no such novel cue was present. Experiment 3 was able to demonstrate this effect. Results are consistent with the Rescorla–Wagner (1972) model of conditioning.

Forebrain monoamines and associative learning: III. The US pre-exposure effect

This experiment evaluated the effects of forebrain norepinephrine (NE) and serotonin depletion on the unconditioned stimulus (US) pre-exposure phenomenon. Rats with either dorsal bundle lesions, raphe lesions, or which served as vehicle controls were assigned to one of two training conditions. One-half of the animals in the 3 lesion groups received 30 episodes of a stimulus which later served as the US. The remaining rats experienced standard conditioning of CS-US pairing without US pre-exposure. The results indicate that while raphe-lesioned and vehicular rats exhibited the US pre-exposure effect, conditioning was unimpaired in NE-depleted rats following pre-exposure. These findings are consistent with a contextual blocking interpretation of the US pre-exposure effect.

Retardation of rabbit nictitating membrane conditioning following US preexposures depends on the distribution and number of US presentations

Retarded conditioned response (CR) acquisition produced by unconditioned stimulus (US) preexposures has been attributed either to interference resulting from contextual conditioning or to habituation of the US. Both perspectives assume that the amount of retardation is directly related to the number of US preexposures. This assumption was examined in two experiments. In Experiment 1, separate groups of rabbits received 200 paraorbital shock US preexposures either in one session or spread equally over 10 daily sessions. Subsequently, all subjects received 150 CS-US pairings. Acquisition of nictitating membrane CRs was retarded relative to a naive control group only in the group that received the preexposures over 10 sessions. Thus, the number of US preexposure sessions, rather than the number of US preexposures, determined whether or not retarded acquisition was observed. In Experiment 2, four groups of rabbits received 1, 5, 20, or 40 shock US preexposures in each of 10 sessions. Over the subsequent 150 CS-US pairings, similar levels of retarded CR acquisition were observed in groups that received 20 and 40 US preexposures per session, a weak retardation effect was observed with 5 preexposures per session, and no retardation was observed with 1 preexposure per session. Thus, Experiment 2 suggested that retarded CR development was not greatly influenced by increasing the number of US preexposures above some minimum threshold number of exposures per session. Implications for current theories were discussed.