The dopaminergic modulation of fear: Quinpirole impairs the recall of emotional memories in rats.

Past studies examining the contributions of dopamine to fear have produced inconsistent results. The present experiments reevaluated this issue. It was found that systemic pretreatment with the D2 agonist quinpirole before pairing 2 conditioned stimuli (CSs; CS2–CS1) dose dependently blocked the acquisition of second-order fear conditioning. Quinpirole's actions were not due to nonspecific impairments in the ability to perceive the CSs, or form and store an association, because the identical drug pretreatment before pairing the same 2 CSs had no effect on the acquisition of sensory preconditioning. In a separate study, rats were given fear conditioning while untreated and then received extinction sessions while under the influence of quinpirole or its vehicle. Quinpirole pretreatment blocked extinction. Findings suggest that quinpirole decreased fear by blocking the retrieval of a learned association between a CS and unconditioned stimulus (UCS), rather than by devaluing the UCS, which would have resulted from summation of quinpirole's appetitive properties with the aversive properties of fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Slow reacquisition following extinction: Context, encoding, and retrieval mechanisms.

Investigated the slow reacquisition (RAQ) of responding in rats that occurs when the conditioned stimulus/stimuli (CS) and unconditioned stimulus/stimuli (UCS) are paired again after prolonged extinction training. In Exp 1, an extinguished CS acquired less suppression than a novel CS during a final conditioning phase, but more suppression than CSs that had received comparable nonreinforcement without initial conditioning. In Exp 2, CS–UCS pairings resumed in the context of extinction caused the least RAQ of suppression: Pairings in a neutral context produced better RAQ, while return of the CS to the conditioning context caused an immediate renewal of responding to the CS. In Exp 3, a return of the CS to the extinction context after RAQ training caused renewed extinction performance and interfered with performance appropriate to RAQ. This effect was not due to demonstrable inhibitory conditioning of the extinction context. Results suggest that representations of conditioning and extinction (or CS–UCS and CS–no UCS relations) are both retained through extinction and that performance appropriate to either phase can be cued by the corresponding context. RAQ may thus be slow when the context retrieves an extinction memory. Similar mechanisms may also play a role in other Pavlovian interference paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative regulation of Pavlovian fear conditioning: Unconditioned stimulus intensity, incentive shifts, and latent inhibition.

Conditional stimuli (CS) associated with painful unconditional stimuli (UCS) produce a naloxone-reversible analgesia. The analgesia serves as a negative-feedback regulation of fear conditioning that can account for the impact of UCS intensity and CS predictiveness on Pavlovian fear conditioning. In Exp 1, training under naloxone produced learning curves that approached the same high asymptote despite UCS intensity. Shifting drug treatment during acquisition had effects that paralleled UCS intensity shifts. In Exp 3, naloxone reversed Hall-Pearce (1979) negative transfer using a contextual CS, indicating that conditional analgesia acquired during the CS–weak-footshock phase retards acquisition in the CS–strong-footshock phase. Exp 5 used a tone CS in both a latent-inhibition and a negative-transfer procedure. Only negative transfer was blocked by naloxone. Therefore, negative transfer but not latent inhibition is mediated by a reduction of UCS processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid reacquisition in conditioning of the rabbit's nictitating membrane response.

Reacquisition after extinction often appears faster than original acquisition. However, data from conditioned suppression studies indicate that this effect may arise from spontaneous recovery and reinstatement of unextinguished contextual stimuli related to the unconditioned stimulus/stimuli (UCS). In the present experiments using the rabbit nictitating membrane preparation, spontaneous recovery was eradicated before reacquisition training. UCS contextual stimuli were controlled by retaining the UCS during extinction through explicit unpairings of the conditioned stimulus/stimuli (CS) and UCS. Attempts were also made to drive the associative strength of the CS into the inhibitory region by differential conditioning and conditioned inhibition procedures. In all cases, reacquisition was very rapid in comparison with a rest control. The results are discussed with respect to their implications for CS and UCS processing models of conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of context on performance to conditioned stimuli with mixed histories of reinforcement and nonreinforcement.

Five conditioned suppression experiments, with 160 Wistar rats, explored the role of the conditioning history of the conditioned stimulus (CS) in determining the effects of contextual fear on performance to the CS. Contextual fear was produced by postconditioning exposure to unconditioned stimulus/stimuli (UCS) alone in the context of conditioning; it was independently assessed with context-preference tests. When the number of reinforced and nonreinforced trials was equated across extinction, partial reinforcement, and latent inhibition procedures, only the extinction procedure produced a CS whose performance was subsequently affected (i.e., augmented) by contextual fear. Contextual fear's relatively unique augmenting effect on fear of an extinguished CS was abolished by extensive, but not by less extensive, reacquisition training. Results indicate that, depending on the CS's conditioning history, contextual fear either augments or has little effect on fear of the CS. It is suggested that augmentation by context should be viewed as the restoration of fear that is otherwise depressed by extinction. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of neurotoxic hippocampal lesions on two effects of context after fear extinction.

Three conditioned suppression experiments with rats examined the role of the hippocampus in 2 effects of context after extinction. Reinstatement is the context-specific recovery of fear to an extinguished conditioned stimulus (CS) that occurs following independent presentations of the unconditioned stimulus (UCS), after extinction. Renewal is the recovery of fear when the CS is presented in the context in which it was conditioned, after extinction in a different context. Results indicated that neurotoxic lesions of the hippocampus, performed before conditioning, abolished reinstatement, which depends on context–UCS associations, but not renewal, which does not. This dissociation is not the result of differences in the recentness of context learning that ordinarily governs the 2 effects. The results suggest that the hippocampus is necessary for some, but not all, types of contextual learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone CS and an aversive footshock unconditioned stimulus/stimuli (UCS). 24 and 48 hrs following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitatory conditioning of individual Drosophila melanogaster..

Demonstrated, in 5 studies, conditioning of the proboscis extension reflex in D. melanogaster. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses (CRs) over trials, (b) measured differences in performance levels among individual Ss, and (c) greater conditioning among males than females. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned stimulus/stimuli (CS) or the unconditioned stimulus/stimuli (UCS) directly affected the CR, whereas UCS preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the UCS. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large samples that can be tested simultaneously on the automated stimulation apparatus, it is suggested that it is now possible to make precise behavioral measurements for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning.

The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for conditioning to an auditory conditioned stimulus/stimuli (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses (CRs). If CS–unconditioned stimulus (UCS) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective UCS during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40–60 trials) using a tone as the CS and medial geniculate complex microstimulation as the UCS. Conditioning bradycardia developed when the UCS electrodes were in the PIN. However, microstimulation was not an effective UCS for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock UCS. Thus, the PIN can be a locus of functional CS–UCS convergence for fear conditioning to acoustic stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Element pretraining influences the content of appetitive serial compound conditioning in rats.

Examined the effects of prior pairings of conditioned stimulus/stimuli (CS)2 with the unconditioned stimulus/stimuli (UCS) on the nature of the associations formed in CS1?→?CS2?→?UCS serial compound conditioning, in 4 experiments with 72 male and 32 female albino rats. In Exps I and II, prior training of CS2 prevented the acquisition of stimulus–stimulus (S–S) associations between CS1 and stimulus features of CS2 but enhanced the acquisition of stimulus–response (S–R) associations between CS1 and the emotional conditioned response (CR) evoked by CS2. In Exps III and IV, the effects of CS2 pretraining were not due to CS2 training itself, but rather to its endowing CS2 with the ability to evoked a strong CR during the early stages of serial compound conditioning. In Exp III, suppression of the CR to a pretrained CS2 during serial compound conditioning permitted the establishment of S–S associations. In Exp IV, the induction of a CR in the presence of an untrained CS2 during serial compound conditioning prevented the acquisition of S–S associations. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioning in panic disorder: Enhanced resistance to extinction.

Enhanced conditionability has been proposed as a crucial factor in the etiology and maintenance of panic disorder (PD). To test this assumption, the authors of the current study examined the acquisition and extinction of conditioned responses to aversive stimuli in PD. Thirty-nine PD patients and 33 healthy control participants took part in a differential aversive conditioning experiment. A highly annoying but not painful electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures were used as either the paired conditioned stimulus (CS+) or the unpaired conditioned stimulus (CS-). Results indicate that PD patients do not show larger conditioned responses during acquisition than control participants. However, in contrast to control participants, PD patients exhibited larger skin conductance responses to CS+ stimuli during extinction and maintained a more negative evaluation of them, as indicated by valence ratings obtained several times throughout the experiment. This suggests that PD patients show enhanced conditionability with respect to extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian conditioned inhibition.

Examined the notion of conditioned inhibition and suggests a definition in terms of the learned ability of a stimulus to control a response tendency opposed to excitation. 2 techniques of measuring inhibition are outlined: (1) the summation procedure in which an inhibitor reduces the response that would normally be elicited by another stimulus, and (2) the retardation of acquisition procedure in which an inhibitor is retarded in the acquisition of an excitatory CR. Examples of the use of these procedures are given for a variety of UCS modalities. Several possible operations for generating conditioned inhibitors are reviewed: extinction following excitatory conditioning, discriminative conditioning, arrangement of a negative correlation between CS and a UCS, use of an extended CS-UCS interval, and presentation of a stimulus in conjunction with UCS termination. These operations suggest that conditioned inhibitors are not generated either by simple extinction procedures or by pairing a stimulus with UCS termination. By contrast, for both salivary and fear conditioning the other procedures do appear to generate inhibitors. Most of the procedures generating conditioned inhibitors can be described as arranging a negatively correlated CS and UCS. (2 p. ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms underlying retarded emergence of conditioned responding following inhibitory training: Evidence for the comparator hypothesis.

The comparator hypothesis posits that conditioned responding is determined by a comparison at the time of testing between the associative strengths of the conditioned stimulus/stimuli (CS) and stimuli proximal to the CS at the time of conditioning. The hypothesis treats all associations as being excitatory and treats conditioned inhibition as the behavioral consequence of a CS that is less excitatory than its comparator stimuli. Conditioned lick suppression by rats was used to differentiate 4 possible sources of retarded responding to an inhibitory CS. These include habituation to the unconditioned stimulus/stimuli (UCS), latent inhibition to the CS, blocking of the CS-UCS association by the conditioning context, and enhanced excitatory associations to the comparator stimuli. Prior research has demonstrated the 1st 3 phenomena. Therefore, we employed parameters expected to highlight the 4th one—the comparator process. In Exp I, our negative contingency training produced a conditioned inhibitor that passed inhibitory summation and retardation tests. In Exp II we found transfer of retardation from an inhibitory CS to a novel stimulus when the location where retardation-test training occurred was excitatory. In Exp III, extinction of the conditioning context attenuated retardation regardless of whether extinction occurred before or after the CS-UCS pairings of the retardation test. Exp IV demonstrated that habituation to the UCS did not contribute to retardation in the present case. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits.

Five experiments examined the effects of iv naloxone treatment on aversive Pavlovian conditioning of eye-blink and heart-rate responses, and related unconditioned behaviors, in 143 male albino rabbits. Naloxone (NX) treatment before testing attenuated bradycardiac orienting responses to tones used as CSs. NX also attenuated conditioned bradycardia when administered either before or after training sessions, but it potentiated conditioned bradycardia during extinction of discriminative conditioning. NX did not influence acquisition or extinction of discriminative eye-blink conditioning or somatic or cardiac responses to shocks used as UCSs, but it did decrease locomotor activity. NX immediately after training sessions facilitated acquisition of eye-blink responses. It is concluded that NX influences aversive Pavlovian conditioning in more than one way: (a) During training, it appears to alter reception and processing of signals but does not affect subsequent development of somatic responses to the Pavlovian conditioning contingency. (b) After training, NX apparently affects consolidation of both somatic and autonomic conditioning. (c) NX also appears to delay extinction of Pavlovian conditioning; this effect may similarly involve changes in a stimulus-processing mechanism or in memory functions, but it apparently does not involve changes in somatomotor responsivity. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian aversive context conditioning using carbon dioxide as the unconditional stimulus.

Four experiments were conducted to examine the utility of carbon dioxide (CO?) as an aversive unconditioned stimulus/stimuli (UCS) in a Pavlovian context conditioning paradigm. Exp 1 demonstrated that rats exposed to CO? in a distinctive context showed elevated levels of freezing relative to controls. Exp 2 replicated this basic effect with a modified conditioning procedure and additionally demonstrated conditioned analgesia. Exp 3 demonstrated a positive monotonic relationship between UCS duration and resistance to extinction of freezing behavior as well as conditioned analgesia. Exp 4 demonstrated extinction and an extinction-related phenomenon, renewal. These studies clearly demonstrate the utility of CO? as a Pavlovian UCS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control by context in the inflation and reinstatement paradigms.

Examined, in 5 conditioned suppression experiments, the influence of summation between fear of the CS and the context in experimental paradigms in which the rat is exposed to UCSs following conditioning or extinction. Context-preference tests assessed contextual fear. In Exps I–III with 88 female Wistar rats, the inflation paradigm, in which fear of a CS paired with a weak UCS is enhanced by exposure to intense UCS alone, was investigated. Results show that the contextual fear that was present when the target CS was tested was reduced by presenting the intense UCSs in a different context, by exposing Ss to the context following their presentation, and by signaling the intense UCSs with a 2nd CS. In Exp IV with 32 female Wistar rats, UCS exposures following conditioning or extinction both produced contextual fear, but only fear of the extinguished CS was reinstated by that fear. In Exp V with 32 female Wistar rats, identical amounts of contextual fear reinstated fear of an extinguished CS, but not a nonextinguished CS, when the 2 types of CSs were arranged to evoke comparable amounts of fear prior to testing. It is suggested that contextual fear plays a role in the reinstatement paradigm but not in the inflation paradigm. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arousal-related associative response characteristics of dorsal lateral geniculate nucleus neurons during acoustic Pavlovian fear conditioning.

This research determined whether fear-conditioned, acoustic stimuli induce thalamic arousal reflected in associative responses in dorsal lateral geniculate nucleus (dLGN) neurons. Rabbits received a Pavlovian discriminative fear conditioning procedure in which one tone conditioned stimulus (CS+) was always paired with an aversive unconditioned stimulus (UCS) and another tone (CS–) was never paired with the UCS. Responses of single dLGN neurons to random CS+ and CS– presentations were then recorded. Nine of 15 recorded neurons demonstrated significantly greater firing during the CS+ versus the CS–. Their spontaneous activity demonstrated tonic firing during increased neocortical arousal and burst firing during decreased neocortical arousal. The results demonstrate that dLGN neurons show associative responses to fear-conditioned, acoustic stimuli and present a model for investigating the neural circuits by which such stimuli affect sensory processing at the thalamic level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human blink startle during aversive and nonaversive Pavlovian conditioning.

Potentiation of blink startle during aversive and nonaversive Pavlovian single-cue conditioning was assessed in human Ss. In Exp 1 (N?=?89), the conditioning group received paired presentations of a visual CS and an unconditioned stimulus/stimuli (UCS), whereas the control group was presented with a random sequence. The UCS was an electric shock for half the Ss and a nonaversive reaction time (RT) task for the other half. Electrodermal conditioning was evident regardless of the nature of the UCS, but blink potentiation was found only in the conditioning group that had been trained with the aversive UCS. These results were replicated in Exp 2 (N?=?65), in which a nonaversive UCS of increased motivational significance was used. Thus, only aversive conditioning seems to affect the affective valence of the CS, at least as reflected by changes in a skeletal reflex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of backward pairings on the conditioning of the albino rabbit's jaw movement and nictitating membrane responses.

Evaluated backward conditioning of appetitive jaw movement and aversive nictitating membrane responses in rabbits, using 3 procedures: test trials, forward acquisition of the same response, and crossmotivational acquisition of the other response system. In both experiments, backward conditioning consisted of 3 conditioned stimulus/stimuli (CS) alone and 22 CS and unconditioned stimulus/stimuli (UCS) pairings. Contrasting the backward conditioning group with explicitly unpaired and no-treatment controls revealed that backward pairings produced no associative effects. The forward acquisition and crossmotivational acquisition tests suggest that excitatory backward acquisition of jaw movement was obtained. The forward acquisition test identified weak inhibitory conditioning of nictitating membrane responses, but the crossmotivational test implicated excitatory conditioning. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats.

The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)