Potentiation of conditioned freezing following dorsomedial prefrontal cortex lesions does not interfere with fear reduction in mice.

In Experiment 1, an auditory conditioned stimulus (CS) was paired with footshock, except when it was preceded by another stimulus (a visual conditioned inhibitor [CI]). After conditioning, all mice displayed less CS-evoked freezing when the CI-CS compound was presented than when the CS was presented alone. However, lesions of the dorsomedial prefrontal cortex (dmPFC) potentiated CS-evoked freezing on each of the 2 sessions (i.e., CI-CS and CS alone). In Experiment 2, mice were submitted to fear extinction (CS-alone presentation for 3 days). Lesioned mice exhibited a higher level of freezing behavior than controls on each of the 3 sessions. However, lesioned mice and controls displayed the same rate of reduction of freezing over the 3 days of extinction. These data in mice support previous studies in rats, which suggests that the dmPFC is not critical for either conditioned inhibition or extinction of acquired freezing behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine attenuation of conditioned autoanalgesia: Implications for theories of situation-specific tolerance to morphine analgesia.

The effect of morphine administration on the development of conditioned autoanalgesia was investigated in four experiments. Animals were administered either morphine or saline and then either exposed or not exposed to nociceptive stimulation. In Experiments 1, 2, and 4 the nociceptive stimulus to which animals were exposed was electric footshock, and in Experiment 3 it was thermal stimulation produced by exposure to a hot plate. It was found that morphine administration attenuated the development of conditioned autoanalgesia produced by exposure to 1 mA shock for 45 s when tests for conditioned autoanalgesia were conducted when animals were under the influence of saline or morphine (Experiments 1 and 2). Morphine also attenuated the conditioned autoanalgesia arising from exposure to 1 mA shock for 15 s, but only when the conditions for the development and expression of conditioned autoanalgesia were made optimal (Experiment 4). Morphine failed to block conditioning when animals were exposed to 2.5 mA shock for 180 s (Experiment 1). Morphine also attenuated conditioned autoanalgesia when animals were exposed to thermal stimulation (Experiment 3), with the degree of attenuation increasing as a function of the intensity of the nociceptive stimulus. The results are discussed in terms of their implications for theories of situation-specific tolerance to the analgesic effect of morphine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unilateral asymptomatic carotid disease does not require surgery

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently shows retarded conditioning when paired with a reinforcer (e.g. footshock) compared with a non-pre-exposed stimulus. This is latent inhibition (LI). Haloperidol-treated animals show potentiated LI, and it has been suggested that this is due to retarded switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that the slowed control of behaviour by the stimulus-reinforcement contingency is due to a haloperidol-induced decrease in the impact, or salience, of the reinforcer, and thus should be antagonized by increasing the impact of reinforcement. Two experiments tested this prediction. In both, LI was assessed using an off-baseline conditioned emotional response procedure in rats licking for water. In Experiment 1, rats were given 10 light pre-exposures and conditioned with two footshocks of either a low (0.5 mA) or a high (1 mA) intensity. In Experiment 2, rats were given 30 pre-exposures and conditioned with either two or five footshocks of 1 mA. In Experiment 1, no-drug controls did not show LI at both shock intensities. Haloperidol (0.1 mg/kg) was ineffective in potentiating LI at low-intensity shock, but produced LI when shock level was increased. In Experiment 2, no-drug controls showed LI with two but not five conditioning trials. Haloperidol was ineffective in potentiating LI with two conditioning trials, but produced LI with five conditioning trials. Although the effect of haloperidol on LI could thus be modified by manipulating shock intensity or the number of conditioning trials, the direction of such modification indicates that the potentiating effect of haloperidol on LI is not in general antagonized by increasing the impact of reinforcement.     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between conditioned and unconditioned flavor preferences.

Five experiments investigated how rats' conditioned preferences or aversions for aqueous odors paired with sucrose or salt are affected by their unconditioned response to those tastes. Rats preferred an odor paired with 30% sucrose over an odor paired with 5% sucrose when both were presented in 5% sucrose, but they showed no preference or, if thirsty, showed the reverse preference, when the odors were presented in 30% sucrose. These changes in conditioned preference corresponded to changes in the rats' unconditioned preference for the accompanying sucrose solution. Rats' conditioned aversions for odors paired with salt showed a similar dependence on their reaction to the accompanying salt solution. The results were interpreted as showing that conditioned and unconditioned flavor preferences combine additively, as if mediated by the same sensory representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar inactivation impairs cross modal savings of eyeblink conditioning.

Eyeblink conditioning using a conditioned stimulus (CS) from one sensory modality (e.g., an auditory CS) is greatly enhanced when the subject is previously trained with a CS from a different sensory modality (e.g., a visual CS). The enhanced acquisition to the second modality CS results from cross modal savings. The current study was designed to examine the role of the cerebellum in establishing cross modal savings in eyeblink conditioning with rats. In the first experiment rats were given paired or unpaired presentations with a CS (tone or light) and an unconditioned stimulus. All rats were then given paired training with a different modality CS. Only rats given paired training showed cross modal savings to the second modality CS. Experiment 2 showed that cerebellar inactivation during initial acquisition to the first modality CS completely prevented savings when training was switched to the second modality CS. Experiment 3 showed that cerebellar inactivation during initial cross modal training also prevented savings to the second modality stimulus. These results indicate that the cerebellum plays an essential role in establishing cross modal savings of eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Counterconditioning of an overshadowed cue attenuates overshadowing.

In 3 Pavlovian conditioned lick-suppression experiments, rats received overshadowing treatment with a footshock unconditioned stimulus such that Conditioned Stimulus (CS) A overshadowed CS X. Subjects that subsequently received CS X paired with an established signal for saccharin (CS B) exhibited less overshadowing of the X–footshock association than subjects that did not receive the X–B pairings (Experiment 1). Experiment 2 replicated this effect and controlled for some additional alternative accounts of the phenomenon. In Experiment 3, this recovery from overshadowing produced by counterconditioning CS X was attenuated if CS B was massively extinguished prior to counterconditioning. These results are more compatible with models of cue competition that emphasize differences in the expression of associations than those that emphasize differences in associative acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus": Correction to McNish et al (2000).

Reports an error in "Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus" by Kenneth A. McNish, Jonathan C. Gewirtz and Michael Davis (Behavioral Neuroscience, 2000[Feb], Vol 114[1], 64-76). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4. (The following abstract of the original article appeared in record 2000-13470-005.) 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased extracellular dopamine in the nucleus accumbens of the rat during associative learning of neutral stimuli

Brain microdialysis was used to study changes in dopamine in the nucleus accumbens and the dorsal striatum during associative learning between two neutral stimuli, flashing light and tone, presented on a paired schedule during stage 1 of a sensory preconditioning paradigm. The tone was subsequently paired with mild footshock using standard aversive conditioning procedures and the formation of a conditioned association between the flashing light and the tone in stage 1 was assessed by measuring the ability of the flashing light to elicit the same conditioned response as the tone when presented at test. The first experiment used behavioural monitoring only, to establish stimulus parameters for subsequent microdialysis experiments. Animals receiving paired presentation of the light and tone in stage 1 showed a conditioned suppression of licking to the light as well as to the tone, indicating that associative learning between the flashing light and the tone had occurred during stage 1, whilst in a separate group of animals given the same stimuli over the same time period but on an explicitly non-paired schedule, the conditioned emotional response was seen to the tone, but not to the light, showing that no association had been formed between the two stimuli during stage 1. In dialysis experiments using the same procedure, we measured a two-fold rise in dopamine in the nucleus accumbens during paired presentation of flashing light and tone, but not during non-paired presentation of the two stimuli. On subsequent test presentation of the two stimuli, we saw increases in accumbal dopamine on presentation of the tone in both groups, reflecting the formation of an association with the footshock in both. However the flashing light elicited an increase in dopamine only in the group which had received paired presentation at stage 1. Thus accumbal dopamine release at test is correlated to the ability of the stimulus to evoke a conditioned response measured behaviourally. Hypotheses of the behavioural function of the mesolimbic dopamine system centre on its role in mediating the effects of biological reinforcers, both rewarding and aversive, conditioned and unconditioned. The present results, showing increases in extracellular dopamine in the nucleus accumbens when an association is formed between two stimuli of which neither is a biological reinforcer nor, prior to formation of the association, affects dopamine levels, suggest a role for accumbal dopamine in the modulation of associative learning in general, not only that involving reinforcement.     

Emotional Conditioning to Masked Stimuli and Modulation of Visuospatial Attention.

Two studies investigated the effects of conditioning to masked stimuli on visuospatial attention. During the conditioning phase, masked snakes and spiders were paired with a burst of white noise, or paired with an innocuous tone, in the conditioned stimulus (CS)+ and CS- conditions, respectively. Attentional allocation to the CSs was then assessed with a visual probe task, in which the CSs were presented unmasked (Experiment 1) or both unmasked and masked (Experiment 2), together with fear-irrelevant control stimuli (flowers and mushrooms). In Experiment 1, participants preferentially allocated attention to CS+ relative to control stimuli. Experiment 2 suggested that this attentional bias depended on the perceived aversiveness of the unconditioned stimulus and did not require conscious recognition of the CSs during both acquisition and expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related differences in short-term retention of separable elements of an odor aversion.

The rate of forgetting over short intervals was tested in preweanling rats, 8, 12, or 18 days postnatal, using procedures that may have analytical advantages over other tests of short-term retention. Separate tests of retention were conducted for the simple occurrence of an odor and for the occurrence of an odor paired with a mild footshock. Forgetting of odors with either of two histories, incidental or target, was more rapid the younger the preweanling, over intervals of less than an hour. There was some indication of more rapid forgetting for incidental than target odors. Finally, although exposure to a CS– (conditioned stimulus [an odor not paired with footshock]) was necessary for conditioning of the CS+ (an odor paired with footshock) in rats 8 or 12 days of age, exposure to a CS– had no influence on conditioning of the CS+ in preweanlings 18 days of age. The age-related differences in forgetting over intervals less than an hour long suggest that substantial age-related differences in forgetting can occur that, it is likely, are not accounted for by differential growth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the retrosplenial cortex in processing multiple conditioned stimuli.

Lesions of retrosplenial cortex (RSP) disrupt spatial and contextual learning, suggesting that RSP may have a fundamental role in processing overlapping, or simultaneously presented stimuli. If so, then RSP lesions might also be expected to disrupt learning that requires the concurrent processing of phasic conditioned stimuli. In Experiment 1, rats were trained in a compound feature negative discrimination task in which a tone was presented and immediately followed by food on some trials, while on other trials a visual stimulus was simultaneously presented along with the tone and not reinforced. Normal rats learned to discriminate between the trials but RSP-lesioned rats exhibited low levels of conditioning on both types of trials. Experiment 2 demonstrated that this effect was not simply due to a general inability to form associations, since RSP-lesioned rats exhibited normal responding when the visual stimulus was presented alone and paired with food. These findings support the view that RSP has an important role in learning that involves the processing of simultaneously presented stimuli and have implications for understanding the functional relationship between the hippocampus and RSP. (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)     

Reactivation treatment prevents the memory-impairing effects of scopolamine in preweanling rats.

The authors report that the expression of a conditioned odor aversion is impaired in preweanling rats when they are conditioned on Postnatal Day 12 and tested under the influence of scopolamine hydrobromide (0.2 or 0.5 mg/kg, intraperitoneal) after a 48-hr, but not after a 2-hr, retention interval (Experiment 1). This effect of scopolamine is not dependent on maturation of the cholinergic system between Days 12 and 14 (Experiment 2), nor is it due to peripheral mechanisms (Experiment 3). When pups are reexposed to the unconditioned stimulus (footshock) before drug administration, performance on the 48-hr retention test is not impaired by scopolamine (Experiment 4). These findings demonstrate that the cholinergic system may be critical for the retrieval and expression of long-term or weak memories in young rats. However, the expression of active memories (recent or recently reactivated) may not be dependent on the cholinergic system to the same extent as is the expression of inactive memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretraining Inactivation of the Caudal Pontine Reticular Nucleus Impairs the Acquisition of Conditioned Fear-Potentiated Startle to an Odor, but Not a Light.

Recent data from developing rats suggest that structures downstream from the amygdala are involved in the acquisition of conditioned fear-potentiated startle (FPS). The authors tested this idea in adult rats by temporarily inactivating the structure critical for FPS, the caudal pontine reticular nucleus (PnC), during fear conditioning. When the conditioned stimulus (CS) was an odor, rats displayed freezing, but not FPS, at test. This effect was not due to a decrease in footshock sensitivity. Further, no savings were evident on retraining. When the CS was a light, inactivation of the PnC had no effect on the acquisition of FPS. Thus, the PnC may be crucial for the acquisition of conditioned FPS to an odor, but not a light. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Amphetamine-induced disruption of latent inhibition depends on the nature of the stimulus

It is well documented that latent inhibition (LI), i.e. slower conditioning to a stimulus that had been repeatedly pre-exposed without consequences, compared to a non-pre-exposed stimulus, is prevented by amphetamine. Recently, we found that the effects of amphetamine on LI, as assessed in an off-baseline conditioned emotional response (CER) procedure, depend on the nature of the pre-exposed stimulus, irrespective of reinforcer intensity. Because these results contrast with a recent finding that a reduction in reinforcer intensity reversed amphetamine-induced attenuation of LI in an on-baseline CER procedure, the present study investigated the effects of amphetamine on LI as a function of the nature of the pre-exposed stimuli and shock intensity, using an on-baseline CER procedure. The effects of amphetamine on post-shock suppression of drinking as well as on activity, were monitored throughout the stages of the CER procedure. Experiment 1 used a 5 s steady light as the pre-exposed and conditioned stimulus, and two shock intensities in conditioning, and Experiment 2 used a 10 s flashing light and two shock intensities. Amphetamine disrupted LI with a steady light at both low and high shock intensities, but failed to disrupt LI with a flashing light at both shock intensities. In addition, the drug disrupted LI in Experiment 3, which increased the duration of the steady light to 10 s and used only low shock intensity, but failed to affect LI in Experiment 4 which used the flashing light on the background of darkness or of light, and only high shock intensity. The effects of amphetamine on LI were not related to its effects on behavioural suppression after footshock, or on activity.     

Involvement of retrosplenial cortex in forming associations between multiple sensory stimuli.

The retrosplenial cortex (RSP) is highly interconnected with medial temporal lobe structures, yet relatively little is known about its specific contributions to learning and memory. One possibility is that RSP is involved in forming associations between multiple sensory stimuli. Indeed, damage to RSP disrupts learning about spatial or contextual cues and also impairs learning about co-occurring conditioned stimuli (CSs). Two experiments were conducted to test this notion more rigorously. In Experiment 1, rats were trained in a serial feature negative discrimination task consisting of reinforced presentations of a tone alone and nonreinforced serial presentations of a light followed by the tone. Thus, in contrast to prior studies, this paradigm involved serial presentation of conditioned stimuli (CS), rather than simultaneous presentation. Rats with damage to RSP failed to acquire the discrimination, indicating that RSP is required for forming associations between sensory stimuli regardless of whether they occur serially or simultaneously. In Experiment 2, a sensory preconditioning task was used to determine if RSP was necessary for forming associations between stimuli even in the absence of reinforcement. During the first phase of this procedure, one auditory stimulus was paired with a light while a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food. During the final phase of the procedure both auditory stimuli were presented alone during a single session. Control, but not RSP-lesioned rats, exhibited more food cup behavior following presentation of the auditory cue that was previously paired with light compared with the unpaired auditory stimulus, indicating that a stimulus-stimulus association was formed during the first phase of training. These results support the idea that RSP has a fundamental role in forming associations between environmental stimuli. (PsycINFO Database Record (c) 2011 APA, all rights reserved)