Differential extinction of 2-way active avoidance in young and adult rats.

Three experiments examined age-related differences in extinction of active avoidance in rats through manipulation of the stimulus context. In Experiment I, 36 weanlings and 36 adults acquired comparable avoidance levels to a tonal conditioned stimulus (CS), and novel stimuli consisting of either the presence of a naive rat or a light were presented during 2 tests in extinction. Results indicated more pronounced disruption of extinction in the pups, compared to adults, with the animate novel stimulus having the greater effect. Eighteen pups of 22 days of age and 18 adults in Experiment II were trained to avoid shock with a CS consisting of simultaneous tone and light onset. During extinction responses did not terminate 1 of the CS elements, but rather produced continuation of either the tone or light for an additional 5 sec. Continuation of the tonal element resulted in greater disruption of extinction trials than the light in the adults, although the pups had faster, but nondifferential, extinction rates. A 3rd experiment presented 36 pups and adults with either 0-, 5-, or 10-sec delays of tonal CS reactivation after extinction responses. Both 5- and 10-sec delays resulted in increased numbers of extinction trials in the adults, but the pups failed to respond differentially to any of the delay intervals. Results of all of the experiments were considered in light of species-specific behaviors in avoidance extinction relative to environmental and associative saliencies between ages.     

Effects of differential cue availability in an active avoidance CS for young and adult rats

In Experiment I, groups of 22- and 140+ -day-old rats were trained in acquisition and extinction of 1-way avoidance with a CS that consisted of the opening of a guillotine door 5 sec before US onset or a combination of door-opening plus a tonal signal that remained on until the occurrence of the motor response. Under both CS conditions, avoidance acquisition was similar at each age level. The extinction data indicated comparable performance for the young subjects but differential performance and greater resistance to extinction for the adult subjects. Adults trained with the door-opening CS persisted in responding for an entire series of 100 extinction trials, whereas the adults trained with the compound CS extinguished well within the 100-trial limit. A 2nd experiment included 10 pre-exposures of the simple or compound CS's prior to avoidance training. Although the pups were insensitive to pre-exposure effects, the adults that were pre-exposed and trained with identical CS'5 showed evidence of pre-exposure effects. Results of both experiments were interpreted as indicative of differential cue saliency between ages.     

The influence of natural preference for tactile stimuli on appetitive learning in rat pups

Stimuli of the same modality tend to be organized along a “natural preference scale.” This study examined the ability of six- and nine-day-old rat pups to acquire appetitive learning, when the CS was one of two differently “naturally preferred” tactile stimuli (floor textures: rug and plywood). In Experiment 1, all pups showed a relative natural preference for the rug texture over the plywood texture. Pups conditioned on the plywood texture (exposed to a sibling pup as the US) showed a robust increase in preference for the conditioned texture whereas pups conditioned on the rug texture showed a different and more moderate pattern of acquisition. Developmental differences were found only in extinction of the conditioned response: six-day-old (but not nine-day-old) pups displayed extinction of the response over four trials. Experiment 2 indicated that preexposure to the rug CS prior to conditioning (latent inhibition) did not interfere with the learning process on the rug texture. Two major alternative explanations for the differential learning patterns are discussed: motivational and catecholaminergic influences on learning. The results suggest that natural preferences may modulate early learning and memory processes. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 29–30, 1997     

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.     

Ontogenetic differences in the effects of unpaired stimulus preexposure on eyeblink conditioning in the rat

Learned irrelevance (LIr) is a Pavlovian conditioning phenomenon in which random or unpaired preexposure to a conditional stimulus (CS) and to an unconditional stimulus (US) retards subsequent paired conditioning involving these stimuli. A previous developmental study of eyeblink conditioning in the rat suggested that LIr is not present on postnatal Day 20. Stanton, Fox, and Carter (1998) showed that unpaired preexposure to a CS and a US on postnatal Day 17 failed to retard (and, in fact, facilitated) subsequent paired conditioning involving these stimuli on postnatal Day 20. The present experiments were designed to further characterize the ontogeny of this phenomenon. In Experiment 1, LIr was observed when rat pups were tested for eyeblink conditioning as described in Stanton et al. (1998), except that preexposure occurred on postnatal Day 27, and acquisition testing occurred on postnatal Day 30. In Experiment 2, preexposure and acquisition both occurred on postnatal Day 30, and four types of preexposure were compared: chamber only, CS alone, US alone, or unpaired presentation of CS and US. Unpaired preexposure impaired acquisition relative to that of the remaining three groups, which did not differ. Experiment 3, showed that under the conditions of Experiment 2, LIr failed to appear on postnatal Day 20, but was observed on postnatal Days 25 and 30. These findings suggest that learning that events are unrelated emerges between postnatal Days 20 and 25 in the rat. Possible behavioral and neural mechanisms underlying this effect are discussed.     

Comparison of the effects of early handling and early deprivation on conditioned stimulus, context, and spatial learning and memory in adult rats

Effects of manipulations of the rat pup-dam relationship on affective learning and memory in adulthood have received scant systematic investigation. The authors previously described how early handling (EH; 15 min isolation/day) and early deprivation (ED; 4 hr isolation/day) exert similar effects on spontaneous adult affect (open-field behavior, acoustic startle, endocrine stress response) relative to nonhandling (NH; C. R. Pryce, D. Bettschen, N. I. Bahr, & J. Feldon, 2001). The present study demonstrates that both EH and ED adults exhibit enhanced active avoidance relative to NH adults. Fear-conditioned context and conditioned stimulus (CS) freezing were unaffected in both EH and ED, but stress hormone responses to the CS were reduced in EH males and ED females relative to NH. In the water maze, ED adults exhibited enhanced spatial learning and memory relative to NH.     

Effects of conditioned stimulus preexposure on human electrodermal conditioning

Two experiments investigated the effects of conditioned stimulus (CS) preexposure on Pavlovian differential conditioning and extinction of the skin conductance response. In both experiments, half the subjects were exposed to 20 presentations each of the CS+ and CS-, and the other half were exposed to control stimuli. CS duration was 8 sec. The unconditioned stimulus in Experiment 1 (N = 48) was a 1000 Hz tone of 80 dB which signalled a reaction time requirement, and in Experiment 2 (N = 48), it was a 1 sec burst of white noise at 105 dB. The results of Experiment 1 indicated that no-preexposure groups displayed more CS+/CS- differentiation than preexposure groups during acquisition and more resistance to extinction, at least for the first interval anticipatory response. In addition, the results of Experiment 2 indicated that no-preexposure groups displayed more differentiation than preexposure groups in terms of the second interval anticipatory response. These data constitute a demonstration of the latent inhibition effect with human subjects, and imply that there is an intrinsic relationship between the orienting response and the conditioning process.     

Effects of Conditioned Stimulus Fear-Relevance and Preexposure on Expectancy and Electrodermal Measures of Human Pavlovian Conditioning

The present research investigated the effects of fear-relevance of the conditioned stimulus (CS) and CS preexposure on human electrodermal conditioning and on a continuous measure of expectancy of the unconditioned stimulus (US). Both experiments employed 20 preexposure, 8 acquisition, and 8 extinction trials in a differential Pavlovian conditioning paradigm with shock as the US. In Experiment 1 (N = 48), electrodermal conditioning was retarded by CS preexposure, but was not influenced by fear-relevance of the CS. Expectancy of the US was retarded by preexposure only in the fear-relevant condition. In Experiment 2 (N = 48), the CS/US contingencies was embedded in a visual masking task. Preexposure retarded both electrodermal conditioning and US expectancy. Neither measure was influenced by fear-relevance of the CS. However, fewer subjects in the preexposure condition learned the CS/US relationship and those who did, did so on later trial than those in the no-preexposure condition. Thus, the results indicated clear retardation of conditioning as a result of preexposure, but no reliable effect of fear-relevance.     

Factors influencing one-trial passive avoidance behavior: implications for studies of retrograde amnesia (RA)

Rats were run in a step-through one-trial passive avoidance task. The effects of preexposure (or familiarization) to the apparatus, prehandling outside of the apparatus, and postshock delay in the apparatus were studied. Preexposure to the apparatus significantly increased one-trial passive avoidance; with no preexposure little passive avoidance learning was obtained. Prehandling did not significantly increase the strength of passive avoidance behavior. Postshock delay did not increase passive avoidance behavior. The results are discussed in terms of their implications for studies of retrograde amnesia (RA) which use one-trial passive avoidance learning.     

Effects of malnutrition and environment on the acquisition and extinction of avoidance behavior in rats

Twelve newborn rats were fed by mothers maintained on a protein-deficient diet (12% casein, M) during lactation, and 12 rats fed by mothers maintained on a diet containing 25% casein were used as controls (C). After weaning, all animals were fed standard lab ration. Half of each group was housed individually (MI and CI), while the other half was allowed to live in pairs (MP and CP). When adult, all animals were trained to avoid footshocks by jumping onto a platform. Training sessions consisted of 40 trials starting with a 20 sec light stimulus (CS) and followed by a 2 sec, 0.6 mA shock (US) with an average intertrial interval of 54 sec. When all animals displayed consistent avoidance behavior, the extinction phase was initiated. The procedure was the same as for the training sessions except that the shock generator was disconnected. Extinction continued until each animal showed a 50% reduction in avoidance performance. During acquisition, MI learned faster than CI and CI showed greater avoidance performance than CP, but no differences were observed between MP and CP. During extinction, group M responded more persistently than group C. The present acquisition results may explain the contradictory data reported in the literature with respect to the effects of malnutrition on avoidance performance, since environmental stimulation was shown to reduce the effects of early malnutrition. Individually housed animals showed greater avoidance performance during both phases.     

Disruption of latent inhibition following systemic administration of parachlorophenylalanine (PCPA).

Rats received either 0 or 30 preexposures to a tone which was later used as a CS in a two-way active avoidance task. Tone preexposure resulted in retarded conditioning in normal animals. This latent inhibition effect, however, was not present in rats treated with parachlorophenylalanine. A second experiment used the combined-cue summation test to verify the fact that stimulus preexposure endowed the tone with latent and not conditioned inhibitory properties. The results were discussed in terms of the role of the serotonergic mesolimbic system in tuning out irrelevant stimuli.     

A comparison between taste avoidance and conditioned disgust reactions induced by ethanol and lithium chloride in preweanling rats

Adult rats display taste avoidance and disgust reactions when stimulated with gustatory stimuli previously paired with aversive agents such as lithium chloride (LiCl). By the second postnatal week of life, preweanling rats also display specific behaviors in response to a tastant conditioned stimulus (CS) that predicts LiCl‐induced malaise. The present study compared conditioned disgust reactions induced by LiCl or ethanol (EtOH) in preweanling rats. In Experiment 1 we determined doses of ethanol and LiCl that exert similar levels of conditioned taste avoidance. After having equated drug dosage in terms of conditioned taste avoidance, 13‐day‐old rats were given a single pairing of a novel taste (saccharin) and either LiCl or ethanol (2.5 g/kg; Experiment 2). Saccharin intake and emission of disgust reactions were assessed 24 and 48 hr after training. Pups given paired presentations of saccharin and the aversive agents (ethanol or LiCl) consumed less saccharin during the first testing day than controls. These pups also showed more aversive behavioral reactions to the gustatory CS than controls. Specifically, increased amounts of grooming, general activity, head shaking, and wall climbing as well as reduced mouthing were observed in response to the CS. Conditioned aversive reactions but not taste avoidance were still evident on the second testing day. In conclusion, a taste CS paired with postabsorptive effects of EtOH and LiCl elicited a similar pattern of conditioned rejection reactions in preweanling rats. These results suggest that similar mechanisms may be underlying CTAs induced by LiCl and a relatively high EtOH dose. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 545–557, 2010.     

Function of ECS as a cue in retrograde amnesia in the rat

Two experiments were performed with rats to examine whether electroconvulsive shock (ECS), which is known to produce retrograde amnesia (RA), would serve as a dominant cue in the training trial. In Experiment I, after 6, 1, or 0 ECS preexposures , rats were received ECS immediately following one-trial passive avoidance training in a step through apparatus. Twenty-four h later, six ECS preexposure group showed a higher level of retention performance. Thus, the effects of ECS on RA were shown to be attenuated by the preexposure to ECS. In Experiment II, it was shown that ECS acquired a considerable amount of cue value which might produce a conditioned suppression on an off-the-baseline type procedure. These results were interpreted as that RA phenomena could be considered as a sort of retroactive conditioning where ECS served as a CS.     

On the participation of hippocampal p38 mitogen-activated protein kinase in extinction and reacquisition of inhibitory avoidance memory

Inhibitory avoidance (IA) learning relies on the formation of an association between stepping down from a platform present in a certain context (conditioned stimulus; CS) with an aversive unconditioned stimulus (US; i.e. a footshock). A single CS-US pairing establishes a robust long-term memory expressed as an increase in step-down latency at testing. However, repeated retrieval of the avoidance response in the absence of the US induces extinction of IA memory. That is, recurring presentation of the CS alone results in a new learning indicating that the CS no longer predicts the US. Although the signaling pathways involved in the consolidation of IA and other fear-motivated memories have been profusely studied, little is known about the molecular requirements of fear memory extinction. Here we report that, as happens with its consolidation, extinction of IA long-term memory requires activity of the p38 subfamily of mitogen-activated protein kinases (MAPK) in the CA1 region of the dorsal hippocampus. Moreover, we found that inhibition of hippocampal p38MAPK blocked memory reacquisition after extinction without affecting either the increase in IA memory retention induced by a second training session or animal's locomotor/exploratory activity and anxiety state.     

Conditioned changes in appetitive and consummatory responses to flavors paired with oral or nutrient reinforcement among adult rats

Recent studies of the behavioral organization of conditioned flavor preferences have suggested the involvement of at least two separate learning systems-an appetitive response system sensitive to the oral hedonic properties of the reinforcer, and a consummatory response system sensitive to its nutrient properties. However, these prior studies were conducted with weanling rats, that differ from adults in terms of their prior experience with food, their learning competencies, and the peculiar ontogenetic constraints on their behavior. It is, therefore, unknown whether flavor preference behaviors are similarly organized in adult rats. In this experiment, adult rats were trained to associate a specific CS flavor with either the sweet taste or the postingestive nutrient effects of sucrose. Conditioned appetitive orienting and consummatory oral responding to the CS flavors were then measured. Unlike weanling rats, adult rats exhibited both conditioned appetitive behavior and conditioned consummatory behavior in response a CS that was previously paired with either oral hedonic or nutrient reinforcement. These results suggest a set of important developmental changes in the neurobehavioral mechanisms of flavor preference learning in the postweaning period.     

Ontogeny of context-specific latent inhibition of conditioned fear: Implications for configural associations theory and hippocampal formation development

Latent inhibition of fear conditioning to an auditory cue, as measured by behavioral freezing, was examined in 18- and 23-day-old rats. In Experiment 1, CS preexposure and conditioning occurred in the same context for some rats but in a different context for other rats, and 24 hr separated CS preexposure and conditioning. The 23-day-old rats showed a context-specific latent inhibition effect, but the 18-day-old rats showed no latent inhibition. In Experiment 2, CS preexposure and conditioning occurred in the same trainining session and both 18- and 23-day-old rats showed latent inhibition. These results were discussed in relation to Wagner's (1976) theory of information processing, hippocampal formation maturation, and function, and Sutherland and Rudy's (1989) configural association theory.©1994 John Wiley & Sons, Inc.     

Sparing of patterned alternation but not partial reinforcement effect after infant and adult hippocampal lesions in the rat

The effect of hippocampal lesions was assessed in patterned (single) alternation (PA) and the partial reinforcement extinction effect (PREE), the two reward-schedule effects that appear earliest in ontogeny. Three groups of rat pups, with appropriate controls, were tested for each effect: lesion as infant/test as infant, lesion as infant/test as adult, and lesion as adult/test as adult. Hippocampal lesions had no effect on PA in any of the three conditions except for a suggestion that the effect was mildly attenuated in the animals given lesions as infants and tested as adults: The pups were able to discriminate rewarded from nonrewarded trials and to inhibit responding on nonrewarded trials. On the other hand, the PREE was eliminated under all conditions of testing, in each case because of an increase in persistence following continuously reinforced acquisition. The results are discussed in terms of the functional maturation of the hippocampus and a possible dissociation of mechanisms that mediate response suppression in PA and in the PREE in infant rats.     

Conditioned flavor avoidance, preference, and indifference produced by intragastric infusions of galactose, glucose, and fructose in rats.

The postingestive reinforcing and satiating effects of intragastric (i.g.) infusions of 16% galactose, glucose, and fructose were compared in adult female rats. In Experiment 1, food-restricted rats were trained to drink (30 min/day) flavored solutions (the CS+Gal and CS+Glu) paired with intragastric (i.g.) infusions of galactose and glucose; other flavors (the CS-) were paired with IG water infusions. In subsequent choice tests, the rats strongly preferred (91%) the CS+Glu to the CS-, but avoided the CS+Gal (21%) in favor of the CS-. In Experiment 2, the rats were trained with a CS+Fru paired with i.g. fructose infusions and a CS- paired with i.g. water. In the choice test they consumed similar amounts of CS+Fru and CS- (CS+Fru preference = 51%). In other choice tests they preferred the CS+Glu (>80%) to CS+Fru and CS+Gal, and the CS+Fru (81%) to CS+Gal. Satiation tests were performed in Experiment 3 by adapting the rats to drink a 3% sugar + 0.2% saccharin solution paired with i.g. water infusions (30 min/day). On different test days 16% sugar instead of water was infused. IG galactose, glucose, and fructose produced comparable reductions in sugar+saccharin intake in the first test session. These findings demonstrate that, while the three sugars had similar satiating effects, they differed substantially in their postingestive flavor conditioning effects. The glucose and fructose results confirm prior data indicating that only glucose generates potent postingestive reinforcing stimuli. The galactose-induced flavor avoidance indicates that this sugar has a negative postingestive consequence. This may be due to the slow and incomplete hepatic metabolism of this sugar in adult rats. Conceivably, galactose intolerance may contribute to the lactose avoidance in adult animals.     

Intertrial responses of rats in two-way avoidance learning to visual and auditory stimuli.

Learning and performance of two-way avoidance were investigated in a total of 68 rats trained with either a visual (change in illumination to darkness or to light) or an auditory (white noise of 70 or 60 dB intensity) conditioned stimulus (CS). Experiment I showed that the darkness CS produce lower avoidance performance and a much higher rate of intertrial responses than either a auditory or a compound (visual plus auditory) CS. A monotonic within-session increase of avoidance performance and a similar, but less regular increase of intertrial responses were found at the beginning of training in each group. In later sessions such trends were observed only in rats trained with a visual CS. Experiments II and III showed also rapid transfer of avoidance response and a corresponding change of intertrial response rate with the change of CS modality. When the compound CS was used, the effects of the visual element were completely overcome by the auditory one. Rats trained with a visual CS in Experiment IV showed a positive correlation between avoidance performance and the number of intertrial responses, which was more pronounced in earlier than in later training sessions. We consider the rise of intertrial behaviour as an adaptive response to the increase of task difficulty. CSi of different modalities differ not only in relative saliency, but also in the discriminability between their onset and offset. The modality of the CS influences not only avoidance performance but also the course of learning.     

Conditioned taste aversion in vasopressin-deficient rats (Brattleboro strain)

Brattleboro rats are homozygous for diabetes insipidus (DI), lacking the ability to synthesize vasopressin. Previous studies reported learning deficits in DI rats on passive avoidance tasks using footshock. Other studies, however, could not replicate these results. In two experiments, we studied the learning of DI and control Long Evans (LE) rats in a different avoidance paradigm: conditioned taste aversion (CTA). In the first experiment a mild CTA to saccharin was established gradually using low levels of an illness-inducing agent (lithium chloride). In the second experiment a strong CTA was established in one acquisition trial and the extinction of the conditioned aversion was followed for 12 trials. The two experiments found no differences between the DI and LE rats in either the magnitude or the rate of acquisition and extinction of the CTA. These results suggest that vasopressin is not involved in the acquisition and retention of CTA, and support previous studies indicating that vasopressin may not be involved in avoidance learning.