Impaired trace and contextual fear conditioning in aged rats.

Trace and contextual fear conditioning were evaluated in adult (3-6 months), early middle-aged (8-12 months), late middle-aged (16-20 months), and aged (24-33 months) Sprague-Dawley rats. After trace conditioning, aged animals exhibited significantly less freezing to the tone conditioned stimulus and training context. Levels of trace-cue and context conditioning were negatively correlated with age (r = -0.56 and -0.59, respectively) and positively correlated with each other (r = +0.52). Aged rats showed robust conditioning in short- and long-delay fear paradigms, suggesting that the trace interval, rather than the use of a long interstimulus interval, is responsible for the aging-related deficits in trace fear conditioning. The authors suggest that these aging-related conditioning deficits furnish useful indices of functional changes within hippocampus or perirhinal cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A short intertrial interval facilitates acquisition of context-conditioned fear and a short retention interval facilitates its expression.

Rats were shocked in a context on two occasions and then tested for fear reactions as indexed by freezing. Rats spent the interval between conditioning trials and between conditioning and test in their home cages. A short interval between context-conditioning trials or between trials involving a discrete conditioned stimulus (CS) produced better learning than longer intervals. A short retention interval between conditioning and test produced better performance than longer intervals. The effects of the intertrial interval on learning are the opposite of those reported previously and are opposite to those predicted by contemporary learning theories. The effects of the training to test interval on performance are predicted by Wagner's sometimes opponent process (SOP) theory (Wagner, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate shock deficit in fear conditioning: Effects of shock manipulations.

Pavlovian contextual fear conditioning occurs when an aversive unconditional stimulus (US), such as a footshock, is presented to a rat shortly after it is placed in an experimental context. Contextual fear conditioning does not occur when the shock is presented immediately upon placement of the rat in the novel chamber. In the present study, the authors report that increasing either the number of immediate shock sessions (Experiment 1) or the immediate shock duration (Experiment 2) did not reverse this deficit. However, immediate shock seems to sensitize subsequent context conditioning (Experiment 3). These findings suggest that the associative deficit produced by immediate shock is not related to the rat's ability to process the footshock US. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Within-subject effects of number of trials in rat conditioning procedures.

D. A. Gottlieb (2008) reported finding no effects of number of conditioning trials in a series of between-subjects magazine approach experiments, when number of sessions and total training time were held constant. This article reports 7 comparable within-subject experiments that looked for effects of number of trials in a variety of conditioning preparations. Experiments 1–3 detected effects of multiplying the number of trials by factors of 4 and 8 in a conditioned magazine approach procedure in which visual and auditory stimuli were paired with food. Experiments 4A and 4B detected effects of a factor of 4 trials in a conditioned flavor preference procedure in which flavors were paired with polycose. Experiments 5 and 6 detected an effect of a factor of 3 trials in a conditioned taste aversion procedure and in a fear conditioning procedure, respectively. Results suggest that variables other than number of trials might play important roles in determining the acquisition of conditioned responding, but effects of number of trials can be detected with sensitive enough procedures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Additional evidence for intact appetitive trace conditioning in hippocampal-lesioned rats.

Hippocampal lesions impair aversive trace conditioning but do not interfere with appetitive Pavlovian trace conditioning of the licking response (LR). This experiment examined whether learning to discriminate the events occurring in the home cage and in the training chamber could account for the differential effects of hippocampal lesions on aversive and appetitive trace conditioning. Performance of rats with excitotoxic lesions of the hippocampus was compared to that of sham-operated rats in LR trace conditioning. The unconditional stimulus (US) “cola soft drink” was delivered only in the training chamber. Thus, as in aversive conditioning procedures, the hedonic properties of the US and the resulting behaviors and motivational states occurred only in that environment. The results failed to reveal learning differences between lesioned rats and controls. Our findings and those of other reports concur that trace conditioning with an appetitive US is independent of the hippocampal system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CS-US preexposure effects on trace eyeblink conditioning in young rats: Potential implications for functional brain development.

Recent studies of delay eyeblink conditioning (EBC) in young rats have demonstrated different effects of various conditioned and unconditioned stimulus (CS-US) preexposure conditions on learning at different ages. The present study extends this research to trace EBC. Subjects experienced 1 of 3 preexposure conditions (paired CS-US, unpaired CS-US, or no stimuli) at either 20 or 24 days of age. Four days later, they were conditioned using either trace (Experiment 1) or delay (Experiment 2) EBC parameters. Results were similar at both ages tested. Paired preexposure facilitated acquisition of delay but not trace relative to context preexposure. Unpaired preexposure impaired acquisition of both delay and trace. These behavioral findings provide a foundation for hypotheses about the functional maturation of cerebellar, hippocampal, and entorhinal learning circuits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Timing in pigeons: Effects of the similarity between intertrial interval and gap in a timing signal.

Previous research suggests that when a fixed interval is interrupted (known as the gap procedure), pigeons tend to reset memory and start timing from 0 after the gap. However, because the ambient conditions of the gap typically have been the same as during the intertrial interval (ITI), ambiguity may have resulted. In the present experiment, the authors found that when ambient conditions during the gap were similar to the ITI, pigeons tended to reset memory, but when ambient conditions during the gap were different from the ITL pigeons tended to stop timing, retain the duration of the stimulus in memory, and add to that time when the stimulus reappeared. Thus, when the gap was unambiguous, pigeons timed accurately. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Massed extinction trials produce better short-term but worse long-term loss of context conditioned fear responses than spaced trials.

A series of experiments studied the effects of the interval between extinction trials on the loss of context conditioned freezing responses. Rats were shocked in one context (A) but not in another (B) and subjected to extinction trials in context A. In Experiment 1, massed trials produced more rapid loss than spaced trials. A shift from spaced to massed trials maintained this loss, but the shift from massed to spaced trials restored lost responses. Experiments 2-5 examined this effect of massed trials on responding across spaced trials. They provided evidence that (a) a single trial was as effective as multiple daily massed trials, (b) learning occurred on the first of the massed trials but not on later ones, and (c) the first trial reduced the amount learned across subsequent massed trials. Finally, alternating extinction trials in A and B produced more response loss across spaced trials than blocks of trials in A and B. The results were discussed in terms of the role accorded to self-generated priming in the models developed by A. R. Wagner (1978, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired trace fear conditioning following neonatal ethanol: Reversal by choline.

Neonatal ethanol exposure in animals results in performance deficits on tests of hippocampus-dependent spatial memory, and recent studies have shown that extra dietary choline can ameliorate some of these impairments. In this experiment, rats were administered 5.25 g/kg ig ethanol per day or sham intubations on Postnatal Days (PD) 4-9 and choline (0.1 ml of an 18.8 mg/ml solution) or saline subcutaneously on PD 4-20. On PD 30, rats were given delay or trace fear conditioning trials and were tested for conditioned stimulus-elicited freezing 24 hr later. Neonatal ethanol produced a profound impairment in trace conditioning that was reversed by choline. Groups did not differ in delay conditioned responding, indicating that neonatal ethanol produces a relatively selective cognitive deficit that can be alleviated with supplemental choline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice.

Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning hippocampus dependent. To determine the trace at which memory consolidation requires the hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, hippocampus dependency of trace conditioning is not related to a bridging function or response timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Music-induced context preference following cocaine conditioning in rats.

Traditional models of drug-seeking behavior have shown that exposure to associated environmental cues can trigger relapse. These learned associations take place during repeated drug administration, resulting in conditioned reinforcement. Although considerable investigation has occurred regarding simple conditioned stimuli, less is known about complex environmental cues, particularly those that may be salient in human addiction. Recent studies indicate that music can serve as a contextual conditioned stimulus in rats and influence drug-seeking behavior during abstinence. The purpose of the present study was to further assess the effectiveness of music as a conditioned stimulus in rats, to determine rats' preferences for two contrasting pieces of music, and to determine rats' preferences for music versus silence. To this end, we created an apparatus that gave instrumental control of musical choice (Miles Davis vs. Beethoven) to the rats themselves. After determining baseline musical preference, animals were conditioned with cocaine (10 mg/kg) to the music they initially preferred least, with alternating conditioning sessions pairing saline with the music preferred most. The animals were subsequently tested in a drug-free state to determine what effect this conditioning had on musical preference. The results indicate that music serves as an effective contextual conditioned stimulus, significantly increasing both musical preference and locomotor activity after repeated cocaine conditioning. Furthermore, we found that rats initially favor silence over music, but that this preference can be altered as a result of cocaine-paired conditioning. These findings demonstrate that, after repeated association with reward (cocaine), music can engender a conditioned context preference in rats; these findings are consistent with other evidence showing that musical contextual cues can reinstate drug-seeking behavior in rats. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Potentiation and overshadowing in Pavlovian fear conditioning.

The present experiments addressed a fundamental discrepancy in the Pavlovian conditioning literature concerning responding to a target cue following compound reinforced training with another cue of higher salience. Experiment 1 identified one determinant of whether the target cue will be overshadowed or potentiated by the more salient cue, namely contiguity between compound CS termination and US presentation. Overshadowing and potentiation were observed with delay and trace procedures, respectively. Experiments 2 and 3 contrasted elemental and configural explanations of potentiation. Both experiments supported a configural account. Experiments 3 and 4, by manipulating prior learning experiences to bias subjects to encode the same compound elementally or configurally, demonstrated decreased potentiation and overshadowing, respectively. Overall, these experiments demonstrate potentiation with nontaste stimuli and identify one variable that determines whether overshadowing or potentiation will occur. Moreover, they show that prior experiences can determine how a compound is encoded and are compatible with the idea of flexible encoding as a principle of information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reasoning rats: Forward blocking in Pavlovian animal conditioning is sensitive to constraints of causal inference.

Forward blocking is one of the best-documented phenomena in Pavlovian animal conditioning. According to contemporary associative learning theories, forward blocking arises directly from the hardwired basic learning rules that govern the acquisition or expression of associations. Contrary to this view, here the authors demonstrate that blocking in rats is flexible and sensitive to constraints of causal inference, such as violation of additivity and ceiling considerations. This suggests that complex cognitive processes akin to causal inferential reasoning are involved in a well-established Pavlovian animal conditioning phenomenon commonly attributed to the operation of basic associative processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 2 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Auditory fear conditioning modulates prepulse inhibition in socially reared rats and isolation-reared rats.

Prepulse inhibition (PPI) is the reduction of the startle reflex when the startling stimulus is shortly preceded by a non-startling stimulus. Previous studies have shown that PPI in rats can be enhanced by auditory fear conditioning (AFC) but weakened by isolation rearing. This study investigated whether isolation rearing affects the effect of AFC on PPI. The results show that PPI was lower in isolation-reared rats than that in socially reared rats, and it was markedly enhanced by AFC in socially reared rats. However, the AFC-induced PPI enhancement in isolation-reared rats was much lower than that in socially reared rats. Moreover, the AFC-induced PPI enhancement was blocked by intraperitoneal injection (1 mg/kg) of the selective antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP), 30 minutes before AFC. The baseline startle was also enhanced by isolation rearing. Thus, isolation rearing impairs not only PPI but also the AFC-induced PPI enhancement, which depends on mGluR5 activity. This study advances the animal model for investigating both neural bases and cognitive features of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpreting the effects of exercise on fear conditioning: The influence of time of day.

Previous studies indicate that physical exercise improves contextual fear memory, as evidenced by increased freezing behavior when rats are returned to a training environment that was initially paired with footshock. However, freezing behavior could also be affected by fatigue, especially because rats were tested shortly after the end of the dark cycle, which is when most wheel running was likely to occur. In addition, exercise has been shown to have anxiolytic effects, further confounding interpretation of the effects of exercise on cognition when using aversive conditioning tasks. These factors were examined in the present study by comparing freezing behavior in exercising and nonexercising rats that were tested at different times in the light cycle. In addition, all rats were tested on an elevated plus maze to assess anxiety-like behavior and in an open-field apparatus to measure locomotor activity in order to directly examine interactions between freezing, anxiety-like behavior, and locomotion. Consistent with prior studies, exercising rats exhibited more context freezing than did sedentary rats when tested early in the light cycle. However, the opposite pattern of results was obtained when testing occurred late in the light cycle, an effect driven by a difference in the amount of freezing exhibited by the sedentary control groups. Indeed, the levels of context freezing exhibited by exercising rats were comparable regardless of when the rats were tested during the light cycle. These data have implications for interpreting the effects of exercise on aversive conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intertrial interval as a contextual stimulus: Further analysis of a novel asymmetry in temporal discrimination learning.

Four experiments investigated discrimination learning when the duration of the intertrial interval (ITI) signaled whether or not the next conditional stimulus (CS) would be paired with food pellets. Rats received presentations of a 10-s CS separated half the time by long ITIs and half the time by short ITIs. When the long ITI signaled that the CS would be reinforced and the short interval signaled that it would not be (Long+/Short?), rats learned the discrimination readily. However, when the short ITI signaled that the CS would be reinforced and the long interval signaled that it would not (Short+/Long?), discrimination learning was much slower. Experiment 1 compared Long+/Short? and Short+/Long? discrimination learning with 16-min/4-min or 4-min/1-min ITI combinations. Experiment 2 found no evidence that Short+/Long? learning is inferior because the temporal cue corresponding to the short interval is ambiguous. Experiment 3 found no evidence that Short+/Long? learning is poor because the end of a long ITI signals a substantial reduction in delay to the next reinforcer. Long+/Short? learning may be faster than Short+/Long?because elapsing time involves exposure to a sequence of hypothetical stimulus elements (e.g., A then B), and feature-positive discriminations (AB+/A?) are learned quicker than feature-negative discriminations (A+/AB?). Consistent with this view, Experiment 4 found a robust feature-positive effect when sequentially presented CSs played the role of elements A and B. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid regulation of Pavlovian overshadowing in fear conditioning.

In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise–light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factors governing single-trial contextual fear conditioning in the weanling rat.

Although contextual fear conditioning emerges later in development than explicit-cue fear conditioning, little is known about the stimulus parameters and biological substrates required at early ages. The authors adapted methods for investigating hippocampus function in adult rodents to identify determinants of contextual fear conditioning in developing rats. Experiment 1 examined the duration of exposure required by weanling rats at postnatal day (PND) 23 to demonstrate contextual fear conditioning. This experiment demonstrated that 30 s of context exposure is sufficient to support conditioning. Furthermore, preexposure enhanced conditioning to an immediate footshock, the context preexposure facilitation effect (CPFE), but had no effect on contextual conditioning to a delayed shock. Experiment 2 demonstrated that N-methyl-D-aspartate (NMDA) receptor inactivation during preexposure impairs contextual learning at PND 23. Thus, the conjuctive representations underlying the CPFE are NMDA-dependent as early as PND23 in the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)