Odor-aversion learning by rats following LiCl exposure: ontogenetic influences

The influence of LiCl preexposure on odor-aversion conditioning produced by an odor-LiCl pairing was studied in rats 7-31 days old. LiCl preexposure interfered with the acquisition of the odor aversion in both young and old pups. The time course of this effect depended, however, on the age of the pups. It lasted much longer (over 24 hr) if pups 8-17 days old were preexposed to LiCl than if the pups were preexposed when 30 days old (less 12 hr). Alternative interpretations of these data were discussed, and it was suggested that the age-dependent differences in the time course of the LiCl preexposed effect may be determined in part by age-related differences in the rat's excretory processes that clear lithium from the circulatory system.     

Latent inhibition in the developing rat: an examination of context-specific effects

Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.     

Stimulus preexposure reduces generalization of conditioned taste aversions between alcohol and non-alcohol flavors in infant rats

Results of 3 experiments showed that infant rats (age 13-17 days) generalize conditioned taste aversions between alcohol and non-alcohol tastes such as a mixture of sucrose and quinine, apple cider vinegar, or coffee. Nonreinforced preexposure to those tastes reduced generalized aversions between them. Generalization between alcohol and sucrose-quinine was reduced not only after preexposure to both tastes, but also when only the nonconditioned taste was preexposed, whereas with alcohol and vinegar, both tastes had to be preexposed to obtain that effect. In no case was generalization reduced when only the to-be-conditioned taste was preexposed. Previous experience with alcohol alone, as well as with similar gustatory stimuli, may enhance subjects' ability to differentiate them during infantile stages in rats.     

Relationship between preexposure to prey and PCPA-induced filicidal activity in Sprague-Dawley rats

Experiments, involving para-chloro-D,L-phenylalanine-induced pup-killing (filicide), were conducted to determine the effect of preexposure to the goal entity on the initial development and long-term expression of PCPA-induced filicide. Three groups of Sprague-Dawley rats (n = 50) were either preexposed/not preexposed, or preexposed for varying periods (5, 8, or 13 days) prior to receiving PCPA. Two major results were obtained: 1) preexposed animals were less filicidal than those not preexposed; and 2) there was an inverse relationship between the number of preexposures and filicide occurrence. The results are interpreted in reference to a serotonin-depletion habituation hypothesis.     

Enhancement of IgE antibody production by ovalbumin aerosol in mice

The effect of aerosolized ovalbumin (OA) on the induction of IgE antibody production was investigated in BALB/c mice. Enhancement of anti-OA IgE antibody production was obtained after the administration of 10 micrograms OA in mice preexposed to 1% aerosolized OA for 6 or 30 min, and after the administration of 1 microgram OA in mice preexposed to aerosolized OA for 30 min. IgE antibody production could also be induced by preexposure to aerosolized OA at a concentration as low as 0.1%. A carrier effect was observed by preexposure to aerosolized OA using a hapten-carrier system. In the latter system, whole body irradiation (200 R) could not enhance IgE response, suggesting that irradiation-sensitive suppressor T cells might be generated in insufficient amount or not at all by aerosolized OA. Preexposure to aerosolized dinitrophenol-OA could not enhance anti-dinitrophenol IgE response. These results suggest that the exposure to aerosolized antigen primed preferentially T helper cells.     

Cingulate cortical coding of context-dependent latent inhibition

Neuronal activity of the auditory thalamus, amygdala, cingulate cortex, and substantia nigra was recorded during the administration of a behavioral test for latent inhibition (LI) or the retardation of behavioral conditioning because of preexposure of the conditional stimulus (CS). Following CS preexposure, both the preexposed CS and a control CS predicted avoidable footshock. LI occurred as significantly fewer avoidance conditioned avoidance responses after the preexposed CS than after the control CS. Attenuation of neuronal responses to the preexposed CS, or neural LI, occurred in all monitored areas. One group of subjects (Oryctolagus cuniculus) then received context extinction, and additional groups experienced novel context exposure or handling. Context extinction enhanced behavioral responding to the preexposed CS, eliminating LI. Context extinction also eliminated cingulate cortical neural LI by enhancing posterior cingulate cortical responses to the preexposed CS and attenuating anterior cingulate cortical responses to the control CS. Present and past results are interpreted to indicate that LI is (a) a failure of response retrieval and/or expression mediated by interfering CS-context associations and (b) a product of interactions of the posterior cingulate cortex and the hippocampus.     

Latent Inhibition and Conditioning in Rat Strains Which Show Differential Prepulse Inhibition

Latent inhibition (LI) is the retardation of associative conditioning resulting from preexposure of the conditioned stimulus (CS) alone prior to conditioning. Schizophrenic patients show deficient prepulse inhibition (PPI) and, at least acutely, deficient LI as well. We recently found that Brown Norway (BN) rats show a PPI deficit compared to Wistar-Kyoto (WKY) rats. If PPI and LI depend on neural processes with common genetic substrates, then LI should be deficient in BN rats as well. Here, LI of a conditioned taste aversion was examined in BN and WKY rats. One group from each strain was preexposed to a saccharin-flavored solution (CS) the day prior to conditioning. For taste aversion conditioning, these two groups again consumed saccharin and were injected with lithium chloride (unconditioned stimulus) 10 min later. A second group from each strain was not preexposed to the CS and was treated identically during conditioning, while a third group was not conditioned (injected with sodium chloride). To test for taste aversion conditioning, saccharin was offered for 20 min/day for 3 days. Nonconditioned BN and WKY rats consumed equal amounts of saccharin on test days. In both strains, conditioned rats showed a saccharin aversion. However, conditioning was less robust in BN than in WKY rats. WKY rats showed good LI of the conditioned taste aversion in that preexposed WKY rats consumed significantly more saccharin on test days than conditioned, nonpreexposed WKY rats. Preexposed BN rats did not consume significantly more saccharin on test days than conditioned, nonpreexposed BN rats. The previously reported deficiency in PPI in the BN rats was confirmed here 1 week after the taste aversion experiment. These results suggest that BN rats show deficient LI as well as PPI and display poor associative learning, a trait also reported in schizophrenia.     

The effects of preexposure to the drug on state dependent retention.

The present experiment examined whether previous experience with a drug would decrease the potential of the drug to produce state dependent retention (SDR) for a passive avoidance response in rats. In the first experiment, a single injection of sodium pentobarbital (20 mg/kg) given on six consecutive days before the training day slightly reduced, but did not block, pentobarbital-induced SDR. In Experiment Two, four preexposure injections of 5 IU/kg insulin reduced the magnitude of memory loss produced by administration of the hormone prior to training. As with pentobarbital, however, preexposure to insulin did not completely block the amnestic effect of the hormone. A subsequent experiment demonstrated that the decrease in the strength of insulin-induced SDR in insulin preexposed rats was not the result of enhanced acquisition. Collectively, these data indicate that noncontingent preexposure to an amnestic treatment may decrease the magnitude of memory loss that would normally result from the administration of that treatment during training.     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus

The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing.     

Postconditioning recovery from the latent inhibition effect in conditioned taste aversion

Two experiments were conducted examining the effects of flavor (CS) preexposure on the retention of conditioned taste aversion. In Experiment 1, rats received preexposure to sucrose solution followed by a sucrose-illness pairing. The expected “latent inhibition” effect was obtained when testing occurred after a two-day but not an eleven-day training-to-test interval. Experiment 2 extended these results by employing five- and twenty-one-day training-to-test interval parameters and provided evidence that the stronger taste aversion displayed by preexposed subjects following long retention intervals is not attributable to differences in training consumption of sucrose solution. This posttraining increase in conditioned taste aversion (CTA) suggests that preexposure blocks expression of memory.     

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. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 808–817, 2012     

The critical role of familiar urine odor in diminishing territorial aggression toward a castrated intruder in mice

Sensory chemo-signals conveying information on sex and familiarity are important to the manifestation of aggressive behaviors in male mice. In this study, we examined the role of familiarity conveyed by urine odor in the induction of aggressive behavior using a resident-intruder paradigm. First, an intact ICR male mouse (resident) was grouped with a castrated DBA mouse (cage-mate) and a female ICR mouse to allow the resident mouse to establish its territory. The resident male showed vigorous aggression, not only toward intact male DBA intruders, but also toward unfamiliar castrated DBA mice (UFC). In contrast, the aggression was markedly reduced toward its castrated DBA cage-mate. Next, to reveal how residents discriminate their cage-mates from unfamiliar intruders, we examined whether urine odor affected this familiarity-related aggression. When part of the body surface of a UFC was swabbed with the urine of a resident's cage-mate, the resident attacked the UFC much less often. These results suggest that the information about familiarity conveyed by urine odor plays an important role in controlling the territorial aggression of a resident male mouse toward castrated intruders.     

Preexposure to (un)predictable shock modulates discriminative fear learning between cue and context: an investigation of the interaction between fear and anxiety

It has been suggested that prior experiences with unpredictable/uncontrollable stressors facilitate subsequent fear learning and the development of anxiety disorders. However, animal research documents that preexposure to unpredictable stressors (USs) impede later fear conditioning with that US. These differential predictions were tested in a human experimental model of clinical anxiety. One (US-only) group was preexposed to unpredictable shocks, a second (Unpaired) group received explicitly unpaired presentations of a neutral shape and the shock, and a third (Paired) group received paired shape-shock presentations. Next, all groups received training with a novel shape, using the same shock (50% reinforcement). Fear responding was assessed through startle modulation and online shock-expectancy ratings. Results showed retarded fear learning in the unpredictable groups compared to the predictable group. We argue that prior experiences of unpredictability may still contribute to the development of clinical anxiety, by impeding adaptive fear learning and perpetuating the perception of unpredictability/uncontrollability.     

Cocaine and ethanol interaction in the conditioned taste aversion paradigm.

The aim of this study was to examine the relationship between cocaine and ethanol in a variant of the conditioned taste aversion (CTA) paradigm. The preexposure CTA procedure formed the basis of the following set of experiments. Experiments 1a and 1b assessed whether cocaine and ethanol were functionally related with overlapping stimulus properties as reflected in the preexposure CTA procedure. Male Wistar rats with restricted water access were preexposed to cocaine or ethanol for 3 consecutive days. Twenty-four hours after the last preexposure session, rats were conditioned to either ethanol or cocaine, respectively. The results of this set of experiments revealed a symmetrical interaction between cocaine and ethanol, where cocaine and ethanol effectively blocked CTA to one another. These findings suggested that there may be overlapping stimulus properties between cocaine and ethanol, which may be detected in this procedure.     

Enrichment to odors improves olfactory discrimination in adult rats

The authors tested how prior odor enrichment affects the spontaneous discrimination of both preexposed and novel odors. Experimental rats were exposed to single odors or to pairs of similar or dissimilar odors for 1-hr periods twice daily over 20 days. Spontaneous discriminations between pairs of similar odors were tested before and after the odor exposure period using an olfactory habituation task. The authors found that (a) experimental rats did not spontaneously discriminate similar odor pairs before the exposure period, whereas they spontaneously discriminated them after the enrichment period, and (b) the improvement of performance was not selective for the odors used during enrichment. These results show that odor experience changes perception in the manner predicted based on other groups' electrophysiological experiments.     

Effect of mother on the development of aggressive behavior in rats.

Young rats 23 days of age (Wistar strain) that are offspring of aggressive parents will attack mice. They kill them, however, only if the mother has already killed mice in their presence. Rats 30 days of age will kill mice spontaneously without any previous exposure to killing. The occurrence of muricide activity in young rats of this age is the same as in the adult population. If offspring of aggressive parents are reared by nonaggressive foster mothers from birth, they will not exhibit the muricide reaction at 30 days. In adulthood, however, the reaction appears to the same extent as in the offspring of aggressive parents reared by aggressive mothers. If the descendants of nonaggressive parents are reared by aggressive foster mothers from birth, 64.7% of them will kill mice at the age of 30 days. This aggression is retained in equal intensity during adulthood and cannot be attributed to specific learning in that the mothers have never encountered a mouse in the presence of their foster young.     

Preexposure to a nonaggressive opponent prevents low-intensity, social-conflict analgesia in mice

In a first experiment, exposure of DBA/2 mice to a small number of attack bites by a C57BL/6 mouse resulted in low-intensity analgesia as assessed by the tail-flick test. The analgesia dissipated within 10 min and was insensitive to naloxone (10 mg/kg, sc) but was antagonized by the irreversible opioid antagonist beta-chlornaltrexamine (5 mg/kg, sc). In a second experiment, preexposure to a nonaggressive C57BL/6 opponent prevented low-intensity analgesia induced by a small number of attack bites 24 hr later. The preexposure effect was abolished by naloxone (10 mg/kg, sc) given before the nonaggressive confrontation. This suggests that the release of endogenous opioids during preexposure interferes with the subsequent activation of endogenous opioid-mediated pain control mechanisms.     

Effects of weasel odor on behavior and physiology of two hamster species

This study examined the behavioral and physiological effects of long-term exposure to overdose of aversive odor (predator odor) in two species of hamsters. About 0.05 mg of anal gland secretions of Siberian weasels (Mustela sibirica) was smeared at the oronasal groove of wild male ratlike hamsters (Cricetulus triton) (natural prey) and laboratory golden hamsters (Mesocricetus auratus) once every day for 4 weeks. After 28 days, the experimental groups of both hamster species displayed higher cortisol level, larger adrenal gland (in ratlike hamsters only), smaller thymus and flank gland, and lower aggression level than the conspecific control group (presented with water). Thus, the long-term presence of overdose of the anal gland secretion of the Siberian weasel could lower the aggression and social rank and suppress the immunity in the hamsters. The reproductive conditions of these prey species, however, seemed not to be affected. In addition, the similarities in the behavioral and physiological responses to the predator odor between the two species of hamsters showed that the responses to predator odor might be innate.     

Familiarity-based stimulus generalization of conditioned suppression in rats is dependent on the perirhinal cortex

We report that bilateral, excitoxic lesions of the perirhinal cortex attenuate rats' familiarity-based stimulus generalization. After surgery, rats were preexposed either to 2 auditory stimuli (A and B) or to only 1 auditory stimulus (B). Following preexposure, all rats received pairings of A and a footshock before assessment of generalized responding (conditioned suppression) to B. Sham rats' generalization was greater when preexposure was to both A and B than when preexposure was to B only. That pattern was abolished in lesioned rats, though no general deficiency was found in other measures of auditory processing. Our findings suggest that the perirhinal cortex is required for rats to encode familiarity as part of stimulus representations.     

Lesions of basolateral and central amygdala differentiate conditioned cue preference learning with and without unreinforced preexposure

In the separated arms conditioned cue preference (CCP) task rats are trained by confining them in one arm of an eight-arm radial maze with food and in another arm on the opposite side of the maze with no food on alternate days. After two such trials, rats prefer the food-paired arm when allowed to move freely between the two arms, neither of which contains food. However, if the rats are preexposed to the maze by exploring it without food before training, no preference is observed and at least 4 training trials are required to produce a CCP, suggesting that unreinforced preexposure to the maze latently inhibits acquisition. If this interpretation is correct, preexposure should reduce the size of the preference acquired with both 2 and 4 training trials. In Experiment 1, this prediction was replicated for 2 training trials; however, with 4 training trials, eliminating preexposure also eliminated the CCP. A previous finding that basolateral amygdala lesions impair the CCP with preexposure and 4 training trials was replicated in Experiment 2, but similar lesions had no effect on the CCP in non-preexposed rats given 2 training trials. In contrast, lesions of the central nucleus impaired the 2 training trial CCP but had no effect on the 4 training trial CCP. This double dissociation suggests that the BLA-mediated 4 training trial CCP may be due to learning about the reward features of the maze space, while the central-nucleus-mediated 2 training trial CCP may be due to a conditioned approach response.