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)     

Specificity of process, response, and stimulus in behavioral bioassays.

Reported 3 experiments which studied aspects of the behavioral specificity of the "biochemical transfer" phenomenon. In Exp I, using 120 common goldfish, an acquisition extract facilitated acquisition but not extinction, while an extinction extract facilitated extinction but not acquisition. In Exp II, using 60 Ss from Exp I and 20 additional Ss, brain extracts facilitated an avoidance response only if they originated in donors that made that same response; extracts from donors that did not respond, although exposed to identical stimuli, did not modify recipient behavior. In Exp III, the biochemical transfer effect was found to be stimulus specific in 48 large and 111 small Ss. Results suggest that the extracts in question are behavior specific and do not generally affect behavior in a global excitatory or global inhibitory way. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrical Stimulation of Medial Prefrontal Cortex Reduces Conditioned Fear in a Temporally Specific Manner.

The authors recently showed that extinction of auditory fear conditioning leads to potentiation of tone-evoked activity of neurons in the infralimbic (IL) subregion of the medial prefrontal cortex, suggesting that IL inhibits fear after extinction (M. R. Milad, & G. J. Quirk, 2002). In support of this finding, pairing conditioned tones with brief (300-ms) electrical stimulation of IL reduces conditioned freezing. The present study showed that IL stimulation inhibits freezing if given 0.1 s after tone onset (the latency of tone-evoked responses) but has no effect if given either 1 s before or 1 s after tone onset. This suggests that IL gates the response of downstream structures such as the amygdala to fear stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of conditioned fear on responsiveness to pain: Long-term retention and reversibility by naloxone.

The effect of a fear CS on responsiveness to pain was examined in 3 experiments with 146 Long-Evans hooded rats. In Exp I, a CS that signaled shock attenuated freezing in response to shock, with the attenuation occurring several minutes after the shock. Naloxone blocked the effect of the CS. The effect of the CS, including its reversibility by naloxone, was retained over a 90-day interval. Exp II showed that this effect on freezing was due to associative fear conditioning rather than blocking of conditioning to context by a novel cue. In Exp III, presenting a fear CS just prior to administering a tailflick (radiant heat) test of nociception increased the tailflick latencies (i.e., the fear CS apparently induced hyperalgesia rather than analgesia). Because this result makes it difficult to interpret the change in freezing observed in Exp I as reflecting antinociception, it raises questions about how pain might differentially affect different measures of pain responsiveness. A memory hypothesis is advanced to resolve the different effects obtained with the freezing and tailflick tests. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear reduction in the rat following central cholinergic blockade.

In the presence of a natural predator, cat, 92 male Long-Evans hooded rats (in 2 experiments) showed a constellation of responses that was used to define fear: freezing, avoiding the cat, and suppressing consummatory behavior. Compared with controls, Ss treated with an anticholinergic drug, scopolamine, showed significantly less freezing and significantly more approach to the cat; further, these Ss actually engaged in consummatory behavior in proximity to the cat. On a 2nd, undrugged exposure to the cat, the original scopolamine-treated Ss continued to show significantly less freezing, more approach, and more drinking than control Ss. Since methyl scopolamine, which mimics the peripheral actions of scopolamine, had no effect on fear responses, these results implicate a central cholinergic system in fear responses or species-typical defense reactions. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of yohimbine on the extinction of conditioned fear: A role for context.

Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats

NMDA receptors in the amygdala seem to be critical for fear conditioning in naive rats. Recent spatial-learning studies suggest that previous learning protected animals from the amnesic effect of NMDA antagonists on new learning (of a similar behavioral task). Therefore, the present study examined whether blocking of NMDA receptors in the basolateral nucleus of the amygdala (BLA) prevents new fear learning in previously fear-conditioned rats, as measured by freezing behavior. Intra-BLA infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) completely blocked fear conditioning to a tone stimulus in animals that had previously been fear-conditioned to a light stimulus. Similar results were obtained with intra-BLA infusions of APV before contextual fear conditioning in rats that had been fear-conditioned to a different context. Additional experiments showed that intra-BLA APV infusions substantially interfere with the expression and extinction of conditioned fear to tone, light, and context stimuli. Together, these results indicate that NMDA receptors in the BLA are crucial for the encoding of new fear memories (i.e., the formation of specific conditioned stimulus-unconditioned stimulus association), the expression of conditioned fear responses, and the extinction of acquired fear.     

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)     

Contextual control of the extinction of conditioned fear: Tests for the associative value of the context.

When male Wistar rats received pairings of a CS with shock in one context and then extinction of the CS in another, fear of the CS was renewed when the CS was returned to and tested in the original context (Exps I and III; 40 Ss). No such renewal was obtained when the CS was tested in a 2nd context after extinction had occurred in the conditioning context (Exp IV; 24 Ss). In Exp II, shocks presented following extinction reinstated fear of the CS, but only if they were presented in the context in which the CS was tested. In each experiment, the associative properties of the contexts were independently assessed. Contextual excitation was assessed primarily with context-preference tests in which Ss chose to sit in either the target context or an adjoining side compartment. Contextual inhibition was assessed with summation tests. Although reinstatement was correlated with demonstrable contextual excitation present during testing, the renewal effect was not. There was no evidence that contextual inhibition developed during extinction. Results suggest that fear of an extinguished CS can be affected by the excitatory strength of the context but that independently demonstrable contextual excitation or inhibition is not necessary for contexts to control that fear. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associations in second-order conditioning and sensory preconditioning.

Conducted 4 experiments using a CER procedure with a total of 120 male Sprague-Dawley rats. Exp. I-III provided demonstrations of 2nd-order fear conditioning and suggest that 2-order conditioning was unaffected by extinction of the 1st-order stimulus upon which it was based. In an analogous sensory preconditioning procedure in Exp. IV, extinction of the 1st-order stimulus did affect responding to the secondary stimulus. Results are inconsistent with an interpretation of 2nd-order conditioning in terms of associations between the 1st- and 2nd-order stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction between drug discriminative stimuli and exteroceptive, sensory signals.

Interactions between drug discriminative stimuli based on 5.6 and 10 mg/kg sodium pentobarbital (ip) and exteroceptive stimuli (visual and auditory) were studied in 27 male Sprague-Dawley rats in a T-maze. In 3 groups, visual stimuli (light vs dark) were differentially paired with drug stimuli; the 4th group discriminated combinations of tonal frequencies (1 kHz or 10 kHz) and the presence or absence of pentobarbital (10 mg/kg). In general, visual stimuli controlled choice behavior (left or right turn) to a greater extent than did the drug training stimuli, whereas the auditory stimuli exerted no apparent control over the pentobarbital stimulus in Group 4. Tests with higher doses (13.75 and 17.5 mg/kg) indicated augmented stimulus control by the drug dimension in 2 groups (Group 1, 10 mg/kg pentobarbital vs saline; Group 2, 5.6 mg/kg vs 10 mg/kg pentobarbital) but not in the 3rd group (5.6 mg/kg pentobarbital vs saline) in the "conflict" situation, in which the exteroceptive conditions signaled one response whereas the drug stimulus signaled the opposite response. Discrimination training with only one of the stimulus dimensions resulted in stimulus control in the following order: 10 mg/kg vs saline?>?5.6 mg/kg vs saline?>?1 kHz vs 10 kHz. This indicates that the auditory stimuli were of marginal significance. It is concluded drugs can compete with exteroceptive, visual stimuli for associative strength. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A role for α?-adrenergic receptors in extinction of conditioned fear and cocaine conditioned place preference.

Previous work has demonstrated an important role for adrenergic receptors in memory processes in fear and drug conditioning paradigms. Recent studies have also demonstrated alterations in extinction in these paradigms using drug treatments targeting β- and α2-adrenergic receptors, but little is known about the role of α?-adrenergic receptors in extinction. The current study examined whether antagonism of α?-adrenergic receptors would impair the consolidation of extinction in fear and cocaine conditioned place preference paradigms. After contextual fear conditioning, injections of the α?-adrenergic receptor antagonist prazosin (1.0 or 3.0 mg/kg) following nonreinforced context exposures slowed the loss of conditioned freezing over the course of 5 extinction sessions (Experiment 1). After cocaine place conditioning, prazosin had no effect on the rate of extinction over 8 nonreinforced test sessions. Following postextinction reconditioning, however, prazosin-treated mice showed a robust place preference, but vehicle-treated mice did not, suggesting that prazosin reduced the persistent effects of extinction (Experiment 2). These results confirm the involvement of the α?-adrenergic receptor in extinction processes in both appetitive and aversive preparations. (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)     

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)     

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)     

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)     

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)     

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)     

D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response.

The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear was investigated in rats using the conditioned emotional response preparation. Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg dose of DCS. However, extinguished fear was "renewed" regardless of the drug treatment when the rats were returned to the context in which fear had been conditioned. Additional results suggest that DCS's facilitation of extinction is a small but meaningful effect in the current method. The results suggest caution regarding the use of DCS as an adjunct to extinction: Although the drug may modestly facilitate extinction learning, it does not necessarily destroy the potential for relapse. Behavioral mechanisms are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory preconditioning in rats following early visual deprivation.

Conducted 3 experiments in which a total of 131 light- and dark-reared (LR and DR) male hooded rats were given sensory preconditioning (SPC). In each experiment, Ss were presented with 2 stimuli either paired or unpaired, followed by conditioning to 1 and extinction on the other. 2 auditory stimuli were used in Exp. I. SPC was found for both LR and DR Ss, with no significant difference due to rearing condition either in acquisition or in the SPC test. In Exp. II, light and tone were employed; SPC was demonstrated and was more effective for LR than DR Ss. In Exp. III, rectangle stimuli were employed. The effect of SPC was evidenced in LR Ss; however, performance of DR Ss was not significantly different from that of controls. Results are discussed in terms of the effect of early visual deprivation on information-processing mechanisms. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)