Sex,stress, and fear: Individual differences in conditioned learning

It has long been recognized that humans vary in their conditionability, yet the factors that contribute to individual variation in emotional learning remain to be delineated. The goal of the present study was to investigate the relationship among sex, stress hormones, and fear conditioning in humans. Forty-five healthy adults (22 females) underwent differential delay conditioning, using fear-relevant conditioned stimuli and a shock unconditioned stimulus. Salivary cortisol samples were taken at baseline and after acquisition training and a 24-h-delayed retention test. The results showed that acquisition of conditioning significantly correlated with postacquisition cortisol levels in males, but not in females. This sex-specific relationship was found despite similar overall levels of conditioning, unconditioned responding, and cortisol. There was no effect of postacquisition cortisol on consolidation of fear learning in either sex. These findings have implications for the understanding of individual differences in fear acquisition and risk factors for the development of affective disorders.     

Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low dosages improves memory in the rat

To ascertain whether very low dosages of pituitary adenylate cyclase-activating polypeptide (PACAP) influence learning in mammals, immediately after the acquisition trial of a passive avoidance response (PAR) paradigm, PACAP-38 was administered intracerebroventricularly at increasing dosages (0, 0.02, 0.2, 2, 20, and 200 ng in 10 microl saline) to different groups of rats. The mnemonic effects were measured by means of retention testing 48 and 96 h later. At intermediate PACAP-38 concentrations there was a significant mnemonic improvement of the PAR. The maximal effect was observed after the 0.2-ng PACAP-38 administration (longer step-through latencies). There was a lesser effect at the subsequent higher concentration, 2 ng. Higher dosages had no effects. It is concluded that PACAP-38 acts as an enhancer of mammalian mnemonic processes even at very low dosages. The positive effect follows an inverted U-shaped dose-response curve. The results may be of interest for the therapy of some neuropathological conditions.     

Postacquisition injection of tetrodotoxin into the parabrachial nuclei elicits partial disruption of passive avoidance reaction in rats.

The recent discovery that post-trial functional blockade of the parabrachial nuclei by intracerebral injection of 10 ng tetrodotoxin (TTX) disrupts acquisition of conditioned taste aversion (CTA) (Ivanova & Bures, 1990a,b) has prompted attempts to ascertain the role of this structure in other types of inhibitory learning. In Experiment 1, rats with implanted parabrachial cannulae were trained in a step-through avoidance task and received bilateral TTX (2 x 10 ng) immediately after the acquisition trial; they displayed significantly weakened avoidance of the shock compartment 2 days later. In Experiment 2, rats were anesthetized with pentobarbital (50 mg/kg) immediately after passive avoidance acquisition and received parabrachial TTX 15 min later; whereas anesthesia alone left the passive avoidance reaction (PAR) unaffected, TTX elicited similar disruption as in unanesthetized animals. In Experiment 3, TTX was injected in anesthetized animals 0, 1, 2, or 4 days after PAR acquisition. The amnesic effect was significant when the acquisition-TTX delay had been prolonged to 24 but not to 48 or 96 h. Since CTA is disrupted by reversible blockade of parabrachial nuclei and of the adjacent reticular formation elicited up to 4 days after acquisition (Ivanova & Bures, 1990b), PAR seems to be impaired to a lesser degree and for a shorter time than CTA by similar TTX treatment.     

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.     

Substantia nigra role in fear conditioning consolidation

The substantia nigra (SN) is known to be involved in the memorization of several conditioned responses. To investigate the role of the SN in fear conditioning consolidation this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats which had undergone fear training to acoustic CS and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way there was no interference with normal SN function during either acquisition or retrieval phases, so that any amnesic effect could be due only to consolidation disruption. The results show that SN functional integrity is necessary for contextual fear response consolidation up to the 24-h after-acquisition delay. On the contrary SN functional integrity was shown not to be necessary for the consolidation of acoustic CS fear responses. The present findings help to elucidate the role of the SN in memory consolidation and better define the neural circuits involved in fear memories.     

Imitation, social facilitation, and the effects of ACTH 4-10 on rats' bar-pressing behavior

The effects of ACTH 4-10 on rats' imitation learning was examined during the acquisition and extinction of a bar-press response for water reinforcement. Rats were exposed to either a bar-pressing conspecific (OB), an experimentally naive conspecific (ON), or an empty box (OE) during bar-press acquisition. In a factorial design, each rat was then exposed to one of the same three conditions during extinction. An 80 mcg dose of ACTH 4-10 was administered to half of the rats in each group prior to observation. Performance differences during acquisition were generally small, but significant performance differences during extinction were found. Social facilitation was indicated by the finding that rats extinguished in the presence of a conspecific exhibited significantly greater resistance to extinction than rats extinguished in the presence of an empty box. An imitation effect was also found. Rats that observed a bar-pressing conspecific during both acquisition and extinction (group OB-OB) showed significantly greater resistance top extinction than did groups OB-ON, CB-OE, or OE-OE. There were no significant effects of the hormone, however, relative to saline controls.     

Effects of extraneous stimulation on afterimage adaptation

Projected afterimages (AI) were measured serially with respect to size, intensity, and color. It was predicted that an acoustic signal administered before completion of the adaptive AI process would cause (1) disruption of ongoing trends, (2) regression to initial trends, (3) prolongation of the adaptive process, and (4) at least some defensive reactions. These predictions were substantiated in a group of 28 subjects compared with a control group of 28. In a second experiment where the signal was administered late in the AI series, only few effects were observed.     

Classical conditioning of blood pressure inMacaca mulatta with cardiac rate controlled

The interaction of heart rate and blood pressure responses was studied in four male rhesus monkeys (M. mulatta) during classical delay conditioning and extinction. During initial conditioning sessions, heart rate was held constant by means of an external cardiac pacemaker; in follow-up conditioning sessions, the heart was free of constraint. Observations were made after these conditioning sessions, (a) during several sessions given over to continued training while different pacing rates were in effect; (b) during a series of extinction sessions in which the heart was paced and unpaced; and, (c) when a heart rate CR was simulated by manipulation of the pacer with no conditioned or unconditioned stimuli present. Throughout all sessions, systolic and diastolic pressures were measured at each heart beat. It was found that blood pressure conditioning was largely unaffected when heart rate changes were prevented during acquisition. Extinction of blood pressure responses was also seen to proceed relatively unimpeded when the heart was paced at a fixed frequency. During the postacquisition conditioning sessions, the several different pacing rates that were tested did not produce any significant differential effects in the blood pressure CRs. Simulated heart rate CRs were accompanied by small changes in pressures, sometimes opposite in direction from the pressure CRs observed during unpaced conditioning trials.     

Effects of cocaine and alcohol, alone and in combination, on human learning and performance.

The acute effects of cocaine hydrochloride (4 to 96 mg/70 kg) and alcohol (0 to 1.0 g/kg), administered alone and in combination, were assessed in two experiments with human volunteers responding under a multiple schedule of repeated acquisition and performance of response chains. Subjects were intermittent users of cocaine and regular drinkers who were not cocaine or alcohol dependent. Alcohol was mixed with orange juice and ingested in six drinks within 30 min; cocaine was administered intranasally 45 min after completion of drinking. In each component of the multiple schedule, subjects completed response sequences using three keys of a numeric keypad. In the acquisition component, a new sequence was learned each session. In the performance component, the response sequence always remained the same. Results were consistent in both experiments, despite variations in the order in which the drugs were tested alone and in combination. Alcohol administered alone increased overall percentage of errors and decreased rates of responding in the acquisition component, whereas responding in the performance component generally was unaffected. Cocaine administered alone decreased rates of responding but did not affect accuracy of responding in the acquisition component, and enhanced accuracy of responding without affecting rates of responding in the performance component. The combined doses of cocaine and alcohol attenuated the effects observed with alcohol and cocaine alone. These results suggest that, under the conditions investigated in this study, (a) alcohol produces greater behavioral disruption than cocaine or cocaine-alcohol combinations, (b) cocaine and alcohol each attenuate effects of the other, and (c) such attenuation is most pronounced for cocaine attenuating the disruptive effects of alcohol.     

Amnesia induced by 2-deoxygalactose in the day-old chick: lateralization of effects in two different one-trial learning tasks

2-Deoxy-D-galactose, an inhibitor of brain glycoprotein fucosylation, was injected intracranially (10 mumole dose in 10 microliters) into either the left or the right forebrain hemisphere of day-old chicks (Gallus domesticus). Bilateral injection of this dose of 2-deoxy-D-galactose is known to induce amnesia for several learning tasks including one-trial passive avoidance and sickness-induced learning. When a tritiated form of the drug was injected into one forebrain hemisphere only, a significantly large proportion of the dose remained in that hemisphere. Chicks were trained in two different one-trial learning tasks. The first was a passive avoidance task in which the chicks were allowed to peck at a green training stimulus (a small light-emitting diode, LED) coated in the bitter liquid, methylanthranilate, giving rise to a strong disgust response and consequent avoidance of the green stimulus. In the second paradigm the chicks were allowed to peck at a similarly colored dry stimulus but, 30 min later, were injected intraperitoneally with lithium chloride (0.1 ml of 1 M solution), causing a sickness-induced aversion for the green LED. 2-Deoxy-D-galactose caused amnesia for the passive avoidance task when injected before training into the right hemisphere but not the left. However, unilateral injection of the drug before training on the sickness-induced learning task did not cause amnesia. The results indicate that fucosylation of brain glycoproteins is required in the right hemisphere for learning the passive avoidance task but that memory for sickness-induced learning can be retained by either hemisphere.     

Ethanol effects on shock-induced fighting and muricide by rats

Ethanol (0.25-1 gm/kg body weight; IP) did not significantly alter shock-induced fighting, regardless of whether it was administered to both rats or to only one rat of the pair. Higher doses tended to decrease shock-induced fighting. Ethanol (0.25-2 gm/kg body weight; IP) also did not induce “nonkiller” rats to kill mice and only high doses (1.5 and 2 gm/kg body weight) decreased the incidence of muricide in “killer” rats. The depressant effects of ethanol on both shock-induced fighting and muricide appeared to result from drug-induced ataxia rather than from a direct effect of ethanol on aggressive behavior.     

Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors

In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-d-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001 and 0.01 μg/rat) did not affect IA memory consolidation. However co-administration of NMDA with ACPA (2 ng/rat) prevented the impairment of IA memory consolidation that was induced by ACPA. Although post-training intra-CeA administration of the NMDA receptor antagonist, d-(−)-2-amino-5-phosphonopentanoic acid (d-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of d-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.     

Variability in the anatomy of the planum temporale and posterior ascending ramus: do right- and left handers differ?

The anatomy of the planum temporale (PT) and posterior ascending ramus (PAR) was studied in vivo in 67 healthy right- and left-handed adults using MRI-based morphometry. The left PT was significantly larger than the right, and there was a weakly significant effect of the right PAR larger than the left. A leftward PT asymmetry was found in 72%, and a rightward PAR asymmetry was found in 64% of the sample. The "typical" configuration of a larger left PT and larger right PAR co-occurred in 56% of the subjects studied, which was only slightly more often than predicted by chance. Eight of 67 subjects had "reversed" PT and PAR asymmetries, with consistent left and mixed handers over-represented in this group. Right PAR size was the only variable that predicted writing hand, and left PT size was the only measure that differed by sex. The left PT was expanded relative to the left PAR in 93% of the sample, suggesting that this configuration may be developmentally regulated and may be a critical substrate for the development of language. These findings demonstrate that important relationships exist between hand preference, and the anatomy of posterior cortical language areas.     

Discrete-Trial Functional Analysis and Functional Communication Training with Three Adults with Intellectual Disabilities and Problem Behavior

We conducted a sequence of two studies on the use of discrete-trial functional analysis and functional communication training. First, we used discrete-trial functional analysis (DTFA) to identify the function of problem behavior in three adults with intellectual disabilities and problem behavior. Results indicated clear patterns of problem behavior for each participant. Second, we used a modified multiple baseline design across participants to assess the effectiveness of functional communication training (FCT) on the acquisition of a replacement communicative response. We conducted postacquisition discrimination probes to evaluate the discriminated use of the new response. Results indicated that FCT was effective in producing acquisition and discriminated use of the replacement response for all participants. The study has relevance because of the empirical evidence of DTFA and its applicability to adults with intellectual disabilities.     

Involvement of dorsal hippocampal α-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task

The present study evaluated the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine-induced amnesia and scopolamine state-dependent memory in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency. Results indicate that post-training or pre-test intra-CA1 administration of scopolamine (1 and 2 μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 μg/rat) was reversed by pre-test administration of the scopolamine that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of α1-adrenergic agonist, phenylephrine (1 and 2 μg/rat) or α2-adrenergic agonist, clonidine improved post-training scopolamine (2 μg/rat)-induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25, 0.5 and 1 μg/rat) or clonidine (0.25, 0.5 and 1 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine. On the other hand, pre-test injection of α1-receptors antagonist prazosin (1 and 2 μg/rat) or α2-receptors antagonist yohimbine (1 and 2 μg/rat) prevented the restoration of memory by pre-test scopolamine. It is important to note that pre-test intra-CA1 administration of the same doses of prazosin or yohimbine, alone did not affect memory retrieval. These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory.     

Scopolamine amnesia of passive avoidance: a deficit of information acquisition

Despite its increasing use as an animal model of memory deficit in human dementia, relatively few studies have attempted to assess the memory processes involved in the anticholinergic-induced impairment of passive avoidance retention. In the present experiments, the influence of scopolamine administered prior to or immediately following training on 24-h retention of step-through passive avoidance was studied in NMRI mice. In low doses (0.3-3.0 mg/kg ip) pretraining administration (-5 min) of scopolamine induced a very strong amnesia. Post-training scopolamine induced a significant effect only at the highest dose tested (30 mg/kg). In a retention test of longer than normal duration (600 vs 180 s), which resulted in a more favorable comparison value in the control group, an intermediate post-training dose (10 mg/kg) induced a small effect which approached significance; a finding which may account for conflicting reports in the literature concerning the ability of scopolamine to induce a post-training deficit. The pretraining effect does not appear to have been solely the result of state-dependent learning; scopolamine (3 mg/kg) administered before both the training and test sessions induced a deficit of approximately the same magnitude as that found when administered before training or before testing only. The results indicate that scopolamine can induce a small post-trial effect, presumably through an influence on consolidation processes. The much larger effect of pretrial scopolamine, however, indicates a primary influence on processes related to information acquisition. Together with findings from the literature, the present experiments suggest that scopolamine-induced amnesia partially, but not completely, models the memory deficits of human dementia.     

Effect of preconditioning unconditioned stimulus experience on learned taste aversions.

One taste-aversion study using male Long-Evans rats in which ethanol was the unconditioned stimulus (UCS) and six studies in which lithium chloride (LiCl) was the UCS demonstrate that (a) exposure to the UCS prior to conditioning retards subsequent acquisition of learned taste aversions; (b) a single preconditioning UCS exposure is sufficient to attenuate conditioning; (c) the preconditioning UCS exposure must occur within a limited period prior to conditioning to attenuate learning; (d) repeated conditioning trials will override the effect of prior exposure to the UCS; (e) tolerance to the UCS is not a necessary condition for the attenuation effect to occur; (f) pairing the preconditioning UCS with a novel flavor other than the CS does not remove the preexposure effect, although it may reduce its magnitude; and (g) the degree of disruption is a positive function of preconditioning UCS dosage and an inverse function of conditioning UCS dosage.     

A comparison of imitation strategies in observational learning of action patterns

The effects of different arrangements of demonstration and imitation of modeled actions on the learning of the 26 handshapes of the American manual alphabet were investigated. A concurrent group (N =16), which imitated handshapes concurrently with their demonstration, was compared with a delayed group (N = 16), which delayed imitation until 3 handshapes had been displayed, and with a combination group (N = 16), which practiced under a combination of concurrent conditions early in acquisition and delayed conditions later in acquisition. Following acquisition, learning was assessed by means of immediate and long-term recall and recognition tests. The delayed group was superior to the concurrent group in long-term serial recall and in immediate and long-term recognition of 3-letter sequences (in nonserial order); the performance of the combination group was between those of the delayed and concurrent groups. Therefore, delaying imitation in acquisition required subjects to expend more cognitive effort to retain and produce handshapes when requested than did concurrent imitation. This was beneficial to development of task knowledge that could be relied on for postacquisition recall and recognition of handshapes.     

A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received less study than NMDA receptors; thus, the reported experiments examined the role of mGluRs in familiarity discrimination in the rat PRH. Experiments 1 and 2 assessed the effects of systemic administration of MPEP, a group I mGluR (specifically mGluR5) antagonist, and/or LY341495, a group II mGluR antagonist, on a spontaneous object novelty preference task. Simultaneous antagonism of both group I and II mGluRs impaired familiarity discrimination following a 24-h but not a 15-min delay, while antagonism of either mGluR subtype alone had no effect at either delay. The impairment was in acquisition, as in Experiment 3 coadministration of MPEP and LY341495 did not affect recognition memory performance when administered either after the sample phase or prior to test. The impairment in long-term recognition memory was mediated by mGluRs in the PRH, as localized intracortical antagonism of group I and II mGluRs also produced a deficit (Experiment 4). No evidence was found for an involvement of group III mGluRs in the acquisition of long-term familiarity discrimination (Experiment 5). These findings establish that glutamatergic neurotransmission in the PRH via group I and II mGluRs is crucial for the acquisition, but not for the consolidation or retrieval of long-term object recognition memory.