Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blocked and overshadowed stimuli are weakened in their ability to serve as blockers and second-order reinforcers in Pavlovian fear conditioning

The ability of a blocked or overshadowed conditioned stimulus (CS) to serve as (a) blocker or (b) a 2nd-order reinforcer in Pavlovian fear conditioning was tested in 152 albino rats. CS-evoked suppression of barpressing for food was the index of conditioned fear. Experiments 1 and 2 showed that an overshadowed CS was weakened in its ability to serve as a blocker. In Experiment 2, a blocked CS was similarly weakened. Experiment 3 showed that an overshadowed and blocked CS was weakened in its ability to serve as a 2nd-order reinforcer. Experiments 4 and 5 failed to restore the blocking ability of blocked (Experiment 4) or overshadowed (Experiment 5) CSs by extinguishing the CSs that had blocked or overshadowed them. Results favor a learning-deficit view of blocking and overshadowing.     

Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning

The present study examined whether the basolateral amygdaloid complex (BLA) participates in the expression of fear conditioned to both an olfactory conditioned stimulus (CS) and the training context. In Experiment 1, pretraining excitotoxic lesions of the BLA abolished immediate postshock freezing, conditioned freezing to an olfactory CS, and conditioned freezing to the training context. Control experiments indicated that lesioned and sham-lesioned subjects did not differ in locomotor activity or in acquisition of a successive-cue odor discrimination task, suggesting that deficits in freezing behavior exhibited by BLA subjects were not due to an impairment in primary aspects of olfaction or to a general enhancement of locomotor activity. In Experiment 2, excitotoxic lesions of the BLA produced either 1 day or 15 days after olfactory fear conditioning abolished both odor-elicited and contextual freezing. Collectively, these data support the notion that the BLA participates in an enduring manner in the expression of conditioned freezing behavior elicited by both olfactory and contextual stimuli.     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats.

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explicitly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ethanol on encoding, consolidation, and expression of extinction following contextual fear conditioning.

Studies of contextual fear conditioning have found that ethanol administered prior to a conditioning session impairs the conditioned freezing response during a test session the next day. The present experiments examined the effects of ethanol on extinction, the loss of conditioned responding that occurs as the animal learns that a previously conditioned context no longer signals shock. Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple (Experiment 2) extinction sessions impaired extinction. Ethanol administered prior to a test session disrupted the expression of freezing after extinction (Experiments 3-5). There was some evidence that ethanol served as an internal stimulus signaling the operation of conditioning or extinction contingencies (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol had no effect on extinction with brief (3 min) or long (24 min) exposures to the context, but injections of 3 g/kg after long exposures impaired extinction. Together, these results indicate that ethanol affects extinction by acting on multiple learning and performance processes, including attention, memory encoding, and memory expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)–unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS–US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and were trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of renewal is dependent on the extinction-test interval rather than the acquisition-extinction interval.

A recent finding suggested that when extinction occurs shortly after acquisition, renewal of an extinguished fear response (fear-potentiated startle) to a light conditioned stimulus (CS) is diminished (Myers, Ressler, & Davis, 2006). The present study attempted to extend this finding using a white-noise CS and freezing as the behavioral measure of fear. In Experiments 1A and 1B, we observed renewal whether extinction occurred 10 min or 24 hr after acquisition. In contrast, renewal was not observed if test occurred 10 min after extinction (Experiment 2). Experiment 3 demonstrated that expression of extinction at the 10-min extinction-test interval was attenuated by a pretest subcutaneous injection of the γ-aminobutyric acid (GABA) inverse agonist FG7142. These findings suggest that renewal is influenced more by the extinction-test interval than the acquisition-extinction interval. Further, the failure to see renewal 10 min after extinction suggests that there is a separate context memory that undergoes a different consolidation function than the CS-no US memory formed during extinction. Finally, the expression of extinction appears to be GABA dependent regardless of the extinction-test interval or the test context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recent Exposure to a Dangerous Context Impairs Extinction and Reinstates Lost Fear Reactions.

Rats were shocked in a context and then exposed to that context in the absence of shock. Shorter intervals between these extinction trials produced more long-term freezing than did longer ones, and shorter intervals between the final extinction trial and test produced more freezing than did longer ones. A short interval between a context extinction trial and test with an extinguished conditioned stimulus (CS) produced more freezing than did a longer one, and a short interval between a nonreinforced context exposure and an extinguished CS reinstated freezing when the CS was tested 24 hr later. The results suggest that recent fear acts to favor subsequent retrieval of the memory formed at conditioning rather than extinction and to render the retrieved memory more salient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overshadowing and stimulus duration.

In 3 experiments, the authors investigated the effect of stimulus duration on overshadowing. Experiments 1 and 2 examined responding to a target conditioned stimulus (CS1) when it was conditioned in compound with a coterminating overshadowing stimulus (CS2) that was longer, shorter, or of the same duration (the long, short, and matched groups, respectively). Equal overshadowing of conditioning to CS1 was obtained in all 3 conditions relative to a control group conditioned to the light alone. There were, however, differences in responding to CS2 as a function of its absolute duration. Experiment 3 examined the contribution of the food-food interval/CS onset-food interval ratio to these findings. In Experiments 1 and 2, the ratio differed for the overshadowing CS but not for the target CS. In Experiment 3, this arrangement was reversed, but the pattern of results remained the same. The implications of these findings for trial-based and real-time models of conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Responses eliminated by noncontingent or negatively contingent reinforcement recover in extinction

Autoshaped key pecking in pigeons was eliminated by presenting reinforcers only during non-CS periods (negatively contingent reinforcement) or in both non-CS and CS periods (noncontingent reinforcement). In either case, when all reinforcers were subsequently removed (simple extinction), responding recovered strongly (Experiment 1). Recovery in extinction occurred only if the CS was in a conditioned state when non-CS reinforcers were introduced (Experiment 2). Recovery from noncontingent reinforcement was virtually complete, since total responding in extinction after response elimination was not less than in control groups extinguished without an intervening response-elimination phase (Experiment 3). Recovery also occurred for nonautoshapable, instrumentally reinforced key pecking (Experiment 4). The hypothesis that recovery is due to reinstatement of the non-CS stimulus conditions of acquisition (absence of food) was not supported (Experiments 5 and 6). Other accounts of recovery are considered.     

Spontaneous recovery of extinguished fear responses deepens their extinction: A role for error-correction mechanisms.

A series of experiments used a within-subject design to study spontaneous recovery of fear responses (freezing) to an extinguished conditioned stimulus (CS) in rats. Experiments 1, 2, 3, and 4 demonstrated that: a remotely extinguished CS elicited more freezing than a recently extinguished one on a common test; that the CS showing recovery underwent greater response loss across additional extinction than the one lacking recovery; and that spontaneous recovery and deepening of response loss survived reconditioning. Experiment 5 demonstrated that an excitor extinguished in compound with a CS showing recovery suffered greater loss than an excitor extinguished in compound with a CS not showing recovery, implying that the differential change is regulated by a common error term. Experiments 6 and 7 demonstrated that extinction of a compound composed of two CSs, one showing recovery and a second lacking recovery, produced greater loss to the CS that showed recovery, implying that the change is also regulated by individual error term. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apparatus Exposure Produces Profound Declines in Conditioned Nictitating-Membrane Responses to Discrete Conditioned Stimuli by the Rabbit (Oryctolagus cuniculus).

The present experiments demonstrated that in the rabbit (Oryctolagus cuniculus) nictitacing-membrane (NM) preparation, exposure to the experimental apparatus produces profound declines in conditioned responding to a discrete conditioned stimulus (CS; Experiments 1, 2A, and 3). Moreover, this decremental effect is at most attenuated in only a minor way when the unconditioned stimulus (US) is presented during exposure to the apparatus (Experiment 2B). Controls for retention loss (Experiments 1 and 3) and for handling and placement in a different context (Experiment 3) did not produce significant declines in responding. These findings challenge theories of extinction that rely primarily on context-US associations but are more consistent with theories that assume context-CS-US associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiated startle: Its relation to freezing and shock intensity in rats.

Two experiments with 47 albino rats measured acoustic startle response and freezing in a potentiated startle paradigm in which a startle stimulus was presented either alone or in the presence of a light conditioned stimulus/stimuli (CS) that had been paired previously with either 1-mA or 3-mA footshock. During the CS, the 1-mA group had higher startle amplitudes and a higher percentage of freezing than the 3-mA group. Startle amplitude was positively correlated with freezing under all conditions. The nonmonotonic relation between potentiated startle and shock intensity replicated the study of M. Davis and D. I. Astrachan (see record 1979-00353-001). However, rather than suppressing startle, as they suggested, freezing facilitated startle and, like startle amplitude, was nonmonotonically related to shock intensity. In Exp II, these results were replicated and showed a regularly decreasing monotonic extinction function or potentiated startle and shock-associated freezing for both shock-level groups. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus Processing and Associative Learning in Wistar and WKHA Rats.

This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.     

Extinction can be enhanced by a concurrent excitor.

Five experiments used rat subjects to investigate the impact on extinction of the presence of other conditioned stimuli. In Experiments 1 (Pavlovian magazine approach) and 2 (instrumental discriminative training), an excitatory stimulus (X) was extinguished alone, in conjunction with a previously reinforced other stimulus (A), in conjunction with previously nonreinforced other stimulus (B), or it was spared extinction. Responding during extinction was greatest to AX, and subsequent testing of X alone showed AX extinction to have produced the most decrement to X. Experiment 3 found similar results using a within-subject design. Experiment 5 continued separate reinforced presentations of A during extinction. This procedure not only promoted extinction of X but also converted it into a conditioned inhibitor. These experiments bear on the mechanisms of overshadowing and stimulus processing, as well as provide information on the determinants of extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery but not reinstatement of the extinguished conditioned eyeblink response in the rat.

Reinstatement—the return of an extinguished conditioned response (CR) after reexposure to the unconditioned stimulus (US)—and spontaneous recovery—the return of an extinguished CR with the passage of time—are 2 of 4 well-established phenomena that demonstrate that extinction does not erase the conditioned stimulus (CS)–US association. However, reinstatement of extinguished eyeblink CRs has never been demonstrated, and spontaneous recovery of extinguished eyeblink CRs has not been systematically demonstrated in rodent eyeblink conditioning. In Experiment 1, US reexposure was administered 24 hr prior to a reinstatement test. In Experiment 2, US reexposure was administered 5 min prior to a reinstatement test. In Experiment 3, a long, discrete cue (a houselight), present in all phases of training and testing, served as a context within which each trial occurred to maximize context processing, which in other preparations has been shown to be required for reinstatement. In Experiment 4, an additional group was included that received footshock exposure, rather than US reexposure, between extinction and test, and contextual freezing was measured prior to test. Spontaneous recovery was robust in Experiments 3 and 4. In Experiment 4, context freezing was strong in a group given footshock exposure but not in a group given eye shock US reexposure. There was no reinstatement observed in any experiment. With stimulus conditions that produce eyeblink conditioning and research designs that produce reinstatement in other forms of classical conditioning, we observed spontaneous recovery but not reinstatement of extinguished eyeblink CRs. This suggests that reinstatement, but not spontaneous recovery, is a preparation- or substrate-dependent phenomenon. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Stimulus competition between a discrete cue and a training context: Cue competition does not result from the division of a limited resource.

Several associative learning theories explain cue competition as resulting from the division of a limited resource among competing cues. This leads to an assumption that behavioral control by 2 cues competing with each other should always reflect a tradeoff, resulting in apparent conservation of total reinforcer value across all competing cues. This assumption was tested in 3 conditioned lick suppression experiments with rats, investigating the effects of changing the conditioned stimulus (CS) duration (Experiment 1), administering pretraining exposures to the CS (Experiment 2), and presenting nonreinforced CSs during the intertrial interval (Experiment 3) on Pavlovian conditioned responding to both the CS and the conditioning context. Fear conditioned to the context and to the CS decreased when the CS was of longer duration, massively preexposed before being paired with the reinforcer, or presented alone during the intertrial interval. These observations are problematic for the theories that explain cue competition as the division of a limited resource and suggest that the total reinforcer value across competing cues is not always fixed for a given reinforcer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)