Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.     

An integrated circuit shock scrambler

The construction of an inexpensive shock scrambler is described. The device uses integrated circuitry to drive switching transistors which, in turn, operate mercury relays. These relays are used to switch high voltage to the shock grids in a standard experimental chamber. The frequency at which shock can be scrambled across the grids can be varied.     

Analysis of sequence-dependent interactions between transient calcium and transmitter stimuli in activating adenylyl cyclase in Aplysia: possible contribution to CS--US sequence requirement during conditioning

An important recent insight in a number of neurobiological systems is that during learning, individual dually regulated proteins with associative properties function as critical sites of stimulus convergence. During conditioning in Aplysia, the Ca2+ /calmodulin-sensitive adenylyl cyclase (AC) in mechanosensory neurons serves as a molecular site of interaction between Ca2+ and serotonin [5-hydroxytryptamine (5-HT)]-two signals that represent the CS and US in these cells. Conditioning requires that the CS and US be paired within a narrow time window and in the appropriate sequence. AC shows an analogous sequence preference: It is more effectively activated when a pulse of Ca2+ precedes a pulse of 5-HT than when the 5-HT precedes Ca2+. One mechanism that contributes to this sequence preference is that Ca2+/calmodulin binding to AC accelerates the rate of AC activation by receptor-Gs. We have identified two additional properties of AC activation that would cause pairing with Ca2+ preceding 5-HT to be more effective than simultaneous pairing or pairing with the reciprocal sequence: (1) Activation of Aplysia AC by a Ca2+ pulse rose with a delay compared with activation by a 5-HT pulse. (2) A late pulse of Ca2+, which arrived after 5-HT, acted, via calmodulin, to accelerate the decay of AC activation by receptor-Gs. Together, these activation properties of AC may contribute to the CS-US sequence requirement of classical conditioning.     

The effects of self-injury on acute negative arousal: A laboratory simulation

Research suggests that performance of non-suicidal self-injury (NSSI) is associated with the reduction of high-arousal negative affect. The present study examined this phenomenon in a laboratory setting. Individuals with a history of NSSI (n?=?39) and non-NSSI controls (n?=?33) underwent an anger induction, and were randomized to self-administer either a high level of electric shock, or a mild shock (control condition) to their upper arm. Consistent with previous research, injurers displayed greater pain analgesia than controls. Contrary to expectations, high shock did not result in enhanced arousal reduction for injurers. However, the high shock led to greater arousal reduction for injurers than controls. Notably, in the high shock condition, higher levels of electrical stimulation (i.e., voltage administered) predicted greater reductions in negative arousal, whereas higher subjective ratings of pain predicted smaller reductions in negative arousal. This pattern suggests that more intense self-inflicted pain facilitates reduction of negative arousal provided the subjective experience of pain is not too aversive. Findings help clarify emotion-regulation models of NSSI.     

Associative vs topographical accounts of the immediate shock-freezing deficit in rats: Implications for the response selection rules governing species-specific defensive reactions

Rats were placed in a novel chamber and were given a single shock, either immediately upon placement in the chamber or after a 2-m delay. During a postshock observation period, delayed shock animals froze while immediate shock rats did not (Experiments 1–5). Additionally, delayed shock animals showed an elevation in defecation, relative to unshocked controls, while immediate shock animals did not (Experiment 1). Freezing and elevated defecation were first found with a 9-s delay between placement and shock, and both responses increased linearly with increasing delays up to at least 81 s (Experiment 2). Immediate shock rats did not show escape-related behaviors when potential escape routes were available (Experiments 3–4). A 2-m preexposure to the chamber, that was separated in time from shock, did not alleviate the immediate shock deficit (Experiments 4–5). The immediate shock deficit was also apparent in a test given 24 h after shock receipt (Experiment 6). If immediate shock rats were later given delayed shock they began to freeze but showed no carryover effects of their prior shock experience (Experiment 6). It was concluded that the immediate shock deficit reflects a deficit in association formation between contextual stimuli and shock rather than a difference in defensive behavioral topography. It also appears that freezing is the dominant conditional response to shock-associated stimuli even though freezing is not unconditionally elicited by the shock itself.     

Conditional withholding of proboscis extension in honeybees (Apis mellifera) during discriminative punishment.

Proboscis extension conditioning of honeybee workers was used to test the ability of bees to respond to appetitive and aversive stimuli while restrained in a harness that allows subjects to move their antennae and mouthparts (Kuwabara, 1957; Menzel, Erber, & Masuhr, 1974). Subjects were conditioned to discriminate between two odors, one associated with sucrose feeding and the other associated with a 10 V AC shock if they responded to the sucrose unconditioned stimulus (US) in the context of that odor. Most Ss readily learned to respond to the odor followed by sucrose feeding and not to the odor associated with sucrose stimulation plus shock. Furthermore, in the context of the odor associated with shock, significantly more subjects withheld or delayed proboscis extension on stimulation with the sucrose US than they did in the context of the odor associated with feeding. Thus, restrained honeybees can readily learn to avoid shock according to an odor context by withholding proboscis extension to a normally powerful releaser. Analysis of individual learning curves revealed that subjects differed markedly in performance on this task. Some learn the discrimination quickly, whereas others show different kinds of response patterns.     

A forty-three day avoidance session

A single Sprague-Dawley rat was subjected to an extended discriminated avoidance session in effect continuously for over 1000 hr (43 days). The longest possible shock-free interval that the subject could obtain without responding was 5 min. Since the subject did not sleep through shock, all resting or sleeping was interrupted at least once every 5 min by either a response or a shock. Neither the experimental (avoidance) animal nor a second animal which received all shocks not avoided by the first, gave any appearance of ill effects from the protracted session.     

A new device for the application of electrical shock

A new apparatus has been developed for the simple, safe, and effective delivery of electric shock. It delivers a single-pulse high-voltage shock of very short duration. Both voltage and current are easily measured and the applied energy can be calculated. Constant energy applications depend less upon skin contact resistance than is the case with 600-V 60-Hz shockers.     

Reinforcement and the organization of behavior in golden hamsters: Punishment of three action patterns

Golden hamsters received free shock (Experiment 1) or they were partially (Experiments 2 and 3) or continuously (Experiments 4 and 5) punished with mild electric shock for face washing, open rearing, or scrabbling. Punishment immediately and enduringly reduced the time engaged in scrabbling and the number and length of its bouts. Face washing was also clearly associated with shock, since effects specific to the contingency between face washing and shock were retained when shock was discontinued, but under some conditions punishment increased the number of bouts of face washing. Open rearing was the most refractory of the three activities to suppression and showed least evidence of retaining the effects of punishment. This pattern of results differs from that found previously when food reinforcement was given for the same activities. It is discussed in terms of constraints on performance of learned associations by a variety of response-specific and reinforcer-specific motivational factors.     

Spatial learning induces differential changes in calcium/calmodulin-stimulated (ACI) and calcium-insensitive (ACII) adenylyl cyclases in the mouse hippocampus

Several lines of evidence indicate that Ca2+/calmodulin-stimulated isoforms of adenylyl cyclase (AC) are involved in long-term potentiation and in certain forms of learning. Recently, we found that training in different types of learning task differentially activates Ca2+-sensitive versus Ca2+-insensitive AC activities in certain brain regions, indicating that AC species other than those stimulated by Ca2+/calmodulin may play an important role in learning processes (Guillou, Rose, & Cooper, 1999). Here, we report the effects of spatial reference memory training in a radial arm maze on the levels of AC1 and AC2 mRNA in the dorsal hippocampus of C57BL/6 mice. Acquisition of the task was associated with a learning-specific and time-dependent increase of AC1 mRNA expression selectively in subfields CA1-CA2. In contrast, AC2 mRNA levels were either reduced or not reliably affected depending on the stage of acquisition. Moreover, no significant changes in AC expression were observed either in the dorsal hippocampus of mice trained in a non-spatial (procedural) version of the task or in cortical regions of mice learning the spatial or procedural task. The regional specificity of these effects indicates that the formation of spatial and non-spatial memory requires distinct contributions from Ca2+-sensitive and Ca2+-insensitive AC in the hippocampus. It is suggested that downregulation of AC2 throughout all hippocampal subfields may play a permissive role during the acquisition of spatial learning whereas an upregulation of AC1 specifically in subfield CA1, may be critical to accurately encode, store or use spatial information.     

Pavlovian counterconditioning is unchanged by chlordiazepoxide or by septal lesions

Two experiments were performed to test whether the minor tranquillizer chlordiaz-epoxide or septal lesions could interfere with Pavlovian counterconditioning. Rats were first trained to bar-press for food on a random interval schedule on which was superimposed the presentation of a light which predicted delivery of a shock. This training continued until all animals were showing stable suppression of responding to the light. Separate groups were then presented, while the manipulandum was retracted from the box, with either a shock paired with the delivery of food or shock and food delivery in a random relationship with one another. This type of intrusion period alternated with the presentation of the light and shock. Pavlovian counterconditioning developed, as shown by progressively less response suppression in the paired groups compared to the random groups. This Pavlovian counterconditioning was in no way reduced by either chlordiazepoxide (5 mg/kg) or by medial or lateral septal lesions. It is argued that these results rule out Pavlovian counterconditioning as a process which is affected by minor tranquillizers or by septal lesions when they interfere with the behavioural tolerance observed after partial punishment or partial reward schedules.     

Attentional control mediates fearful responding to an ecologically valid stressor

Background and Objectives: Attentional control (AC) is defined as the ability to voluntarily shift and disengage attention and is thought to moderate the relationship between preexisting risk factors for fear and the actual experience of fear. Design: This longitudinal study elaborates on current models of AC by examining whether AC moderates or mediates effects of an ecologically valid stressor (a college examination) and also whether AC is predictive of state-like fear over longer timescales than previously reported. Methods: Based on previous findings, we hypothesized that AC would moderate the relationship between trait anxiety and affective distress in response to the examination stressor. We also tested a competing mediational model based on AC theory. These models were tested in two separate samples (sample 1, N = 219; sample 2, N = 129; Total N = 348) at two time points, at the beginning of a college semester in a large undergraduate class and 5 minutes prior to a college examination. Results: Mediation but not moderation of anxiety by AC was supported in both samples using multiple dependent measures. Conclusions: We conclude that AC may be useful in predicting affective distress in naturalistic settings, particularly in cases where anxiety is anticipatory.     

Naloxone and shock-elicited freezing in the rat.

The freezing behavior of the rat that occurs following painful electric shock was found to increase when the animal was pretreated with the opiate antagonist naloxone. Freezing was a positive linear function of drug dose and shock intensity (Experiment 2). Naloxone pretreatment enhanced freezing only when the animal was given two or three shocks but did not affect freezing when the animal was given only one shock or not shocked at all (Experiments 3, 4, and 5). Naloxone must be present during shock, nor just during the observation period, in order to increase freezing (Experiment 6). These results suggest that when an animal is shocked, it releases endogenous analgesics (endorphins) that make a subsequent shock less aversive. Naloxone, by blocking the endorphin system, makes the shock more aversive than it would normally be.     

Rats learn the relationship between responding and environmental events: An expansion of the learned helplessness hypothesis

Previous research has shown that preexposure to inescapable shock interferes with subsequent acquisition of escape responding, while pretraining with escapable shock facilitates subsequent acquisition of a different escape response. It has also been demonstrated that interference and facilitation persist when the aversive event is changed between the two phases of training. The present experiment extended these findings, showing generalized learning from an appetitive to an aversive situation. Six groups of rats received the following treatment in the presence of discriminative stimuli: One group was trained to nose press for food, a second to chain pull for food, and a third to chain pull to escape or avoid shock. Two groups received either signalled free food or inescapable shock, and a naive control group received no pretreatment. All groups were then tested in a nose-press escape-avoidance situation. The three groups with prior response training acquired responding most rapidly, and at the same rate. The naive controls acquired responding slowly, and the two groups with response-independent histories did not acquire responding during the 5 days of training. It was concluded that rats learn the relationship between responding and environmental events and that such learning strongly influences subsequent learning.     

Associative independence revisited: competition between conflicting associations can be resolved or even reversed in one trial

In one type of association-memory paradigm, after studying pairs of the form AB, AC, participants must recall both B and C in response to A. Counterintuitively, yet often replicated, recall probabilities of B and C are typically uncorrelated (“associative independence”). This face-value independence is now understood to reflect a negative correlation due to AB and AC competing, approximately offset by a positive correlation produced by subject- and item-variability. The outcome might vary with stimulus material; for noun-pairs, and with a single study trial per pair, AB and AC have been found to be positively correlated. We replicated the positive correlation between AB and AC for noun-pairs, but this did not differ from the correlation expected for independent memory tests, suggesting that for noun pairs, AB and AC are independent on average. In Experiment 2, participants instructed to form separate images for AB and AC again produced an independence pattern, but participants instructed to combine AB and AC into an integrative image produced a facilitation pattern. Thus, the relationship between AB and AC varies, and can be influenced by study strategy. Association-memory models may need to accommodate a diverse range of AB–AC relationships, and studies that build on AB/AC learning may need to consider whether AB/AC start out with a competitive, facilitatory or independent relationship.     

Prior exposure to inescapable electric shock in rats affects extinction behavior after the successful acquisition of an escape response

In Expt 1, rats exposed to 64 inescapable electric shocks in a restrainer or merely restrained were later given either 0, 5, 15 or 30 escape/avoidance training trials with a two-way shuttlebox procedure that does not lead to interference with escape acquisition due to prior exposure to inescapable shock. After escape training all rats were given an escape/avoidance extinction procedure in which shock was inescapable. The rats which had received prior exposure to inescapable shock responded less often and with longer latencies in extinction than did the restrained rats. Experiment 2 demonstrated that this effect is caused by the inescapability of the initial shock treatment. These results were explained in terms of (a) associative interference which minimized the effect of shuttlebox escape training for the preshocked subjects, and (b) a stronger tendency to recognize the presence of an inescapable shock situation during extinction for the preshocked subjects. The relationship between these results and previous work demonstrating that exposure to the escape contingency mitigates the effects of inescapable shock exposure was also discussed.     

Infusion of lidocaine into the dorsal hippocampus before or after the shock training phase impaired conditioned freezing in a two-phase training task of contextual fear conditioning

Learning in a contextual fear conditioning task involves forming a context representation and associating it with a shock. The dorsal hippocampus (DH) is implicated in representing the context, but whether it also has a role in associating the context and shock is unclear. To address this issue, male Wistar rats were trained on the task by a two-phase training paradigm, in which rats learned the context representation on day 1 and then reactivated it to associate with the shock on day 2; conditioned freezing was tested on day 3. Lidocaine was infused into the DH at various times in each of the two training sessions. Results showed that intra-DH infusion of lidocaine shortly before or after the context training session on day 1 impaired conditioned freezing, attesting to the DH involvement in context representation. Intra-DH infusion of lidocaine shortly before or after the shock training session on day 2 also impaired conditioned freezing. This deficit was reproduced by infusing lidocaine or APV (alpha-amino-5-phosphonovaleric acid) into the DH after activation of the context memory but before shock administration. The deficit was not due to drug-induced state-dependency, decreased shock sensitivity or reconsolidation failure of the contextual memory. These results suggest that in contextual fear conditioning integrity of the DH is required for memory processing of not only context representation but also context-shock association.     

Attentional control moderates fearful responding to a 35% CO(2) challenge

Attentional control (AC) is an individual difference variable indexing the ability to voluntarily focus attention and shift attention when desired. AC is thought to impact the experience of fear by facilitating the disengagement of attention from threat and promoting the deployment of attentional resources toward regulatory or coping strategies. Whereas previous research has focused on visual threat cues, in the current study we examined whether this model also applies to interoceptive threat by evaluating the extent to which individual differences in AC moderated the relationship between trait anxiety and self-reported fear in response to a single vital capacity inhalation of a 35% CO(2), 65% balanced O(2) gas mixture. The sample comprised a large nonclinical group of young adults (N=128). Results indicated that AC moderated the relationship between trait anxiety and fearful responding to the challenge. Findings suggest that AC plays a significant and clinically important role in modulating self-reported fear.     

Preconditioning exposure to the unconditined stimulus affects the acquisition of a conditioned emotional response

Four experiments examined the UCS preexposure phenomenon using conditioned suppression of food-reinforced responding as a measure of excitatory conditioning, and electric shock as a UCS. In Experiment 1, groups of rats were preexposed to unsignaled 0.8-mA electric shocks for 0, 1, 3, 5, or 10 days, and then conditioned with a 0.8-mA electric shock. Preexposure to electric shock 1 day prior to conditioning enhanced the acquisition of a CER, whereas preexposure to electric shock for 3, 5, or 10 days prior to conditioning attenuated the acquisition of a CER as a direct function of the number of days of preexposure. In Experiments 2 and 2A, groups of rats were preexposed to unsignaled electric shocks of 0.3, 0.5, 0.8, or 1.3 mA for 10 days, and then conditioned with a 0.8-mA electric shocl. All groups preexposed to electric shock acquired the CER at a slower rate than a group not preexposed to electric shock. The greatest attenuation of CER conditioning occurred when the same intensity electric shock was used during both the preexposure and conditioning phases. In Experiment 3, groups of rats were preexposed to signaled electric shocks of either 0.5, 0.8, or 1.3 mA, and then conditioned with a 0.8-mA electric shock. All groups preexposed to electric shock acquired the CER at a slower rate than a group not preexposed to electric shock. As in Experiments 2 and 2A, the greatest attenuation of CER conditioning occurred when the same intensity electric shock was used during both the preexposure and conditioning phases. In Experiment 4, groups of rats were preexposed to series of 0.5, 0.8, or 1.3-mA electric shocks which they could escape by performing a chain-pull response. Rats in each of these groups had yoked partners which received the same number, intensity, and temporal pattern of electric shocks, but could not perform a response to escape shock. All groups were then conditioned with a 0.8-mA electric shock. Rats preexposed to escapable electric shocks showed equal or greater attenuation of CER conditioning than rats which could not escape shock during the preexposure phase. These results are discussed in terms of nonassociative and associative explanations of the UCS preexposure phenomenon.     

Processing of logically valid and logically invalid conditional inferences in discourse comprehension

Two competing theories of processing of conditionals (if-then) were tested. Syntactic theories posit that people only draw inferences conforming to the logically valid modus ponens (MP) schema. Mental models theories predict that people draw MP and invalid affirming-the-consequent (AC) inferences. Three experiments tested these predictions. Participants read short stories that conformed to either the MP or AC form but without conclusions, and they completed either priming or recognition tasks. Results indicate that both MP and AC inferences occur during discourse processing: MP and AC premise forms prime their respective conclusions, participants erroneously judged that they had read the conclusions to MP and AC arguments, and AC inferences did not stem from a biconditional interpretation of conditionals. Findings support mental models theories.