Conditioned Suppression Procedure Research Articles

Muscimol-induced inactivation of the anterior cingulate cortex does not impair trace fear conditioning in the rat.

Previous studies suggest that trace conditioning depends on the anterior cingulate cortex (ACC). To examine the role of ACC in trace fear conditioning further, 48 rats were surgically prepared for infusion with saline or 62.5 or 125 µg/side muscimol to inactivate ACC reversibly prior to conditioning. A noise stimulus was followed by a 1 mA footshock, with or without a 10-second trace interval between these events in a conditioned suppression procedure. The trace-conditioned groups (10 seconds) showed less test suppression than the control-conditioned groups (0 seconds). Counter to prediction, there was no effect of muscimol infusion on suppression to the noise stimulus in the 10-second trace groups.

Extinction of inhibition after serial and simultaneous feature negative discrimination training.

Two experiments using a conditioned suppression procedure with rats found that following training, nonreinforced presentations of an inhibitory feature stimulus (X) had different effects, depending on whether a serial (A+, XA−) or a simultaneous (A+, A→X−) feature negative discrimination procedure was used to establish the inhibition. Those presentations exhanced X's inhibitory power after simultaneous feature negative training, but reduced X's inhibitory power after serial feature negative training. These data suggest that the nature of inhibition established in feature negative discriminations depends on the temporal arrangement of stimuli.

Ketamine administration diminishes operant responding but does not impair conditioned fear

While not well understood, the NMDA (N-methyl-D-aspartate) antagonist ketamine, a dissociative anesthetic, has been reported to be efficacious in depression and related psychological disorders. Conditioned fear is a normal emotional conditioning process that is known to become dysfunctional in individuals suffering from Post-Traumatic Stress Disorder (PTSD) and related stress disorders. We examined the effects of ketamine to determine the potential modulation of the acquisition and extinction of a conditioned fear using a conditioned suppression procedure. Rats were trained on a variable interval (VI), food maintained, operant conditioning task to establish a general measure of performance. Rats were exposed to inescapable shock (IES, unconditioned stimulus) paired (×20) with an audio/visual conditioned stimulus (CS) to establish conditioning. Conditioning was quantified by measuring response suppression following CS presentation during subsequent extinction trials where the CS alone was presented. Ketamine or vehicle was administered either after initial conditioning or after each of the subsequent extinction trials. For each regimen, a series of four injections were administered 60min apart (100, 50, 50, 50mg/kg, respectively) in order to sustain a ketamine effect for a minimum of 4h. Ketamine produced a general decrease in responding on the VI, relative to baseline, as response rates were slower on the operant task when tested 24h later and longer. Ketamine did not affect the acquisition of the conditioned fear when the regimen was administered shortly after the initial pairings of IES and CS. Ketamine did not alter extinction to the conditioned fear when the regimen was administered following each CS only presentation following initial conditioning. Our conclusion from these findings is that while ketamine alters behavior on an appetitively motivated operant task it does not, however, appear to directly modulate learning and memory processes associated with conditioned fear.

Effects of stimulus salience on the magnitude of latent inhibition after compound conditioning.

The effect of stimulus salience on latent inhibition (the retardation of conditioning produced by prior exposure to the event to be used as the conditioned stimulus [CS]) was examined in an experiment using rats as subjects and the conditioned suppression procedure. The stimuli were a more salient light and a less salient tone-rats trained with light as the CS showed more suppression than rats trained with the tone as the CS; and rats tested with tone and light separately after conditioning with a CS consisting of a tone + light compound showed more suppression to the light than the tone. This pattern of results was reversed, however, in subjects given a series of nonreinforced presentations of the tone and the light separately prior to conditioning with the compound. We conclude that latent inhibition develops more readily for the more salient stimulus and that its effects can outweigh those that derive from the intrinsic salience of the stimulus. Theories of latent inhibition that predict, or can accommodate, this conclusion are considered.

Effects of dietary choline availability on latent inhibition of flavor aversion learning

ObjectiveIt has been previously reported that dietary choline supplementation might affect latent inhibition (LI) using a conditioned suppression procedure in rats. We have assessed the effect of dietary choline on LI of flavor aversion learning.MethodAdult male Wistar rats received a choline supplemented (5 g/kg), deficient (0 g/kg), or standard (1.1 g/kg) diet for 3 months. After this supplementation period, all rats went through a conditioned taste aversion (CTA) procedure, half of them being pre-exposed to the conditioned stimulus before the conditioning.ResultsThe results indicated that choline deficiency prevents LI of conditioned flavor aversion to cider vinegar (3%) induced by a LiCl (0.15 M; 2% body weight) intraperitoneal injection, while choline supplementation enhances CTA leading to slower extinction.DiscussionThe role of the brain systems modulating attentional processes is discussed.

Effect of pharmacological manipulations of neuropeptide Y and corticotropin-releasing factor neurotransmission on incubation of conditioned fear

We recently developed a procedure to study fear incubation in which rats given 100 tone-shock pairings over 10 days show low fear 2 days after conditioned fear training and high fear after 30 or 60 days. Here, we studied the role of the stress-related peptides, neuropeptide Y (NPY) and corticotropin-releasing factor (CRF), in fear incubation. We gave rats either 10 or 100 30-s tone–0.5-s footshock pairings over 1 day (short training) or 10 days (long training) and then assessed tone-cue-induced conditioned suppression of lever responding 2 days after short training or 2 days and 1 month after long training. Prior to testing, we injected NPY (5–10 μg, i.c.v.), the NPY Y1 receptor antagonist BIBO3304 (20–40 μg, i.c.v.), the NPY Y2 receptor antagonist BIIE0246 (2.5–5 mg/kg s.c.), the non-selective CRF receptor antagonist D-Phe CRF(12–41) (10 μg, i.c.v.), or the CRF1 receptor antagonist MTIP (10–20 mg/kg s.c.). Conditioned suppression after long training was higher after 1 month than after 2 days (fear incubation); conditioned suppression was robustly expressed 2 days after short training (non-incubated fear). Both incubated and non-incubated fear responses were attenuated by NPY. In contrast, D-Phe CRF(12–41), MTIP, BIBO3304, or BIIE0246 had no effect on conditioned fear at the different time points. Results confirm previous work on the potent effect of exogenous NPY administration on conditioned fear, but the negative results with BIBO3304 and BIIE0246 question whether endogenous NPY contributes to incubated (or non-incubated) fear. Results also suggest that CRF receptors are not involved in cue-induced fear in the conditioned suppression procedure.

Overshadowing and CS duration: counteraction and a reexamination of the role of within-compound associations in cue competition.

In the present experiments, we examined the role of within-compound associations in the interaction of the overshadowing procedure with conditioned stimulus (CS) duration, using a conditioned suppression procedure with rats. In Experiment 1, we found that, with elemental reinforced training, conditioned suppression to the target stimulus decreased as CS duration increased (i.e., the CS duration effect), whereas, with compound reinforced training (i.e., the overshadowing procedure), conditioned suppression to the target stimulus increased as CS duration increased. In subsequent experiments, we replicated these findings with sensory preconditioning and demonstrated that extinction of the overshadowing stimulus results in retrospective revaluation with short CSs and in mediated extinction with long CSs. These results highlight the role of the duration of the stimulus in behavioral control. Moreover, these results illuminate one cause (the CS duration) of whether retrospective revaluation or mediated extinction will be observed.

Fear of the warning signal during overtraining of avoidance

The present experiment assessed the Pavlovian properties of a tone used as a warning signal in discrete-trial avoidance training of rats by measuring its ability to block conditioning to a light when the tone-light compound signalled shock in a conditioned suppression procedure. The results, although based on a different measure of Pavlovian conditioning, confirmed those reported by Starr and Mineka (1977). After moderate levels of avoidance training, the tone blocked conditioning to the light; but after extended avoidance training it no longer did so, even though a yoked group exposed to the same Pavlovian relation between tone and shock showed no such decline.

A Context-Specific Latent Inhibition Effect in a Human Conditioned Suppression Task

Three studies used a computer video game preparation to demonstrate latent inhibition in adult humans. In all studies participants fired torpedoes at a target spaceship by clicking the mouse. Conditioned stimuli (CSs) were presented in the form of coloured "sensors" at the bottom of the screen. Conditioning was conducted by pairing a sensor with an attack from the target spaceship. Participants learned to suppress their rate of mouse clicking in preparation for an attack. In Experiment 1 a total of 10 preexposures to the sensor CS, prior to conditioning, retarded acquisition of suppression. In Experiment 2 the effect of preexposure was shown to be context specific. Experiment 3 showed little generalization of the preexposure effect from one sensor CS to another. Experiment 3 also showed that preexposure did not make the sensor CS inhibitory. Comparisons with conditioned suppression procedures with animals and negative-priming procedures are briefly discussed.

Systemic or intra-accumbens injection of D-amphetamine delays habituation to a tone stimulus in rats

Dopamine release within the nucleus accumbens shell is suggested to control the salience of environmental stimuli, and previous research has shown that the indirect dopamine agonist D-amphetamine can alter the salience of both aversive and neutral stimuli. In experiment 1, the effect of systemic injection of D-amphetamine (0.5, 1 mg/kg) on fear conditioning to a tone was assessed in an 'off-baseline' conditioned suppression procedure using several footshock intensities. Although the effects of amphetamine on conditioning were unclear, the results indicated a deficit of simple tone habituation in amphetamine-treated rats. In experiment 2, habituation of the orienting reaction to a tone was assessed by the progressive reduction of lick suppression upon repeated presentation of the auditory stimulus. D-Amphetamine delayed tone habituation, whether administered systemically (0.5, 1 mg/kg) or into the nucleus accumbens shell (3, 10 microg/0.5 microl). These data are consistent with electrophysiological and neurochemical data demonstrating the role of nucleus accumbens dopamine in novelty processing. The relevance of the data to latent inhibition is discussed.

Retrospective revaluation effects in the conditioned suppression procedure

In four experiments using the conditioned suppression procedure, rats received initial reinforced training with two compound stimuli, AX and BY, each compound consisting of one auditory and one visual element. After a second phase of training consisting of nonreinforced presentations of A, the suppression governed by X and Y was tested. In Experiment 1 X evoked slightly less suppression than Y (a mediated extinction effect). This outcome was obtained when the auditory cues served as X and Y(Experiment 1a), when the visual cues served as X and Y(Experiment 1b), and when the number of nonreinforced presentations of A was increased (Experiment 1c) from 18 to 216. In Experiment 2, however, in which the initial training was given with serial compounds (i.e., A --> X and B --> Y) X evoked more suppression than Y (a recovery-from-overshadowing effect). It was argued that extinction of A engages two learning processes, one increasing the effective associative strength of its associate (X) and one reducing it, and that the balance between these two depends on the specific conditions of training.

GABA transmission in the ventral pallidum is not involved in the control of latent inhibition in the rat

Latent inhibition describes a process of learning to ignore stimuli of no consequence, and is disrupted in acute, positive-symptomatic schizophrenia. Understanding the neural basis of latent inhibition in animals may help to elucidate the neural dysfunction underlying positive schizophrenic symptoms in man. Evidence suggests a crucial role for dopamine transmission in the nucleus accumbens in the control of latent inhibition. The present studies investigated the role of the GABA-ergic efferent from the nucleus accumbens to the ventral pallidum in latent inhibition. The GABA A agonist muscimol (4.56 ng/μl), and antagonist picrotoxin (0.2 μg/μl), were infused into the ventral pallidum, and effects on latent inhibition were assessed using a conditioned suppression procedure. Neither drug produced specific effects on latent inhibition when given alone and, in the case of muscimol, failed to reverse the disruption of latent inhibition induced by systemic amphetamine. In addition to significant non-specific drug effects, a positive control experiment revealed that intra-pallidal picrotoxin significantly enhanced locomotion, suggesting that our manipulations of ventral pallidal GABA function were behaviourally effective. We conclude that modulating ventral pallidal GABA transmission does not affect latent inhibition. The implications of this finding for theories of the neural circuitry mediating latent inhibition and for understanding the functional role of ventral pallidal GABA transmission are discussed.

Effect of the 5-HT 6 receptor antagonists Ro04-6790 and Ro65-7199 on latent inhibition and prepulse inhibition in the rat: comparison to clozapine

In the present study, we have investigated the effects of two selective 5-HT 6 receptor antagonists, Ro04-6790 and Ro65-7199, in three drug-induced models of PPI disruption and on latent inhibition (LI) utilizing a conditioned lick suppression (CLS) procedure. Clozapine was included in each experiment for comparison. Neither Ro04-6790 nor Ro65-7199 (both 30 mg/kg) affected the PPI disruption produced by PCP (1.5 mg/kg sc), apomorphine (0.1 mg/kg sc), or LSD (0.1 mg/kg sc). There was also no interaction between each drug and CS preexposure in the CLS test indicating a failure of each drug to facilitate LI. In contrast, clozapine (12 mg/kg) attenuated an apomorphine and PCP-induced PPI deficit, although the PPI disruption produced by LSD was not significantly affected. At a lower dose of 5 mg/kg, clozapine also facilitated LI. Since each of these tests bear some predictive validity for the detection of antipsychotic drugs, the present studies do not support a therapeutic potential of 5-HT 6 receptor antagonists in this regard.

Conditioned Suppression With Cocaine as the Unconditioned Stimulus

A conditioned-suppression procedure was used to study drug conditioning using cocaine as the unconditioned stimulus (UCS). Rats were first trained to nose poke for food-reinforcement during daily 60-min sessions. At least 1 week following jugular vein catheterization, a 5-min tone–light compound stimulus was presented 30 min into the food-reinforcement session. Two minutes after the onset of the stimulus, either 0 (saline), 1.0, 3.0 or 5.6 mg/kg cocaine, was administered IV to separate groups of rats. For another group, the stimulus was presented, and the 5.6 mg/kg dose of cocaine was injected in an unpaired fashion (i.e., at different times). After 5 days of training a test was given with the tone–light stimulus presented alone. No disruption of responding during the tone–light stimulus was observed in the saline and 1.0 mg/kg cocaine groups or for the unpaired group. When the tone–light stimulus was paired with 5.6 mg/kg cocaine; however, it produced nearly a 50% reduction in responding, which then gradually extinguished when the stimulus was presented alone for 5 days. The 3.0 mg/kg cocaine group produced intermediate suppression. When the tone–light compound stimulus was shortened to 70 s and the interstimulus interval (ISI) was 0, 30, or 60 s in three separate groups of rats, the most robust conditioned suppression was observed at the 60 s ISI. Therefore, the conditioned suppression procedure, using 3.0 or 5.6 mg/kg IV cocaine doses as the UCS, produced robust conditioning effects comparable to other drugs and more conventional reinforcers. The conditioned suppression procedure may be a useful model for studying the classically conditioned effects of cocaine.

Attenuation of latent inhibition after compound conditioning

Using a conditioned suppression procedure with rats, three experiments examined the effects of compound conditioning on the degree of latent inhibition. Experiment 1 suggested that latent inhibition of the preexposed target was not enhanced but rather attenuated when a second stimulus was presented in compound conditioning. Experiment 2 showed that a similar result was obtained when, in subjects given only compound conditioning, the salience of the target was reduced to the level where it was overshadowed by the second stimulus. Experiment 3 proved that addition of the second stimulus only during preexposure, or during both preexposure and conditioning, did not attenuate the latent inhibition to the target. These results are difficult to explain by any model of Pavlovian conditioning which assumes that both latent inhibition and overshadowing effects are a consequence of acquisition deÞcit; other possible accounts are discussed.

WAY100635 and latent inhibition in the rat: selective effects at preexposure

The influence of the selective, silent 5HT1a antagonist WAY100635 (Wyeth Research Ltd) on the latent inhibition effect was examined in a within-subject, on-baseline conditioned suppression procedure in rats. WAY100635 was found to enhance the latent inhibition effect, producing a retardation in the acquisition of conditioned suppression following a level of stimulus preexposure known to be insufficient to produce a latent inhibition effect in control animals. This influence of the drug was restricted to its actions during the preexposure phase of the experiment, and the drug also abolished the unconditioned suppression of lever pressing that occurs on the first presentation of a novel auditory stimulus. These findings are discussed in terms of the possible influence of serotonergic manipulations on contextual processing, and also have important implications for current animal models of schizophrenia which stress the role of dopaminergic mechanisms in latent inhibition.

Video Display for Study of Avian Visual Cognition: From Psychophysics to Sign Language

We demonstrated four different ways of using video systems for research in avian visual cognition: 1) recent developments of high vision TV systems made it possible to use the video system for psychophysical studies. Visual acuity measured with such a video system was comparable to those obtained by more traditional methods; 2) using image processing software, we could display unnatural animals, such as chimeras on the TV screen. We also reported that pigeons did not discriminate partially occluded conspecifics; 3) effects of exposure to visual stimuli upon on-going behavior were examined using suppression and conditioned suppression procedures; and 4) discrimination of moving images, namely two words of Japanese Sign Language, are reported.

Contextual Control of Latent Inhibition by the Reinforcer

Three experiments examined the contextual control of latent inhibition (LI) by the unconditioned stimulus (US) using a within-subjects conditioned suppression procedure with rats. The effect of reducing the context change produced by the introduction of the shock US was investigated by presenting this US during preexposure to the conditioned stimulus (CS). Although limited CS preexposure in the absence of the US had no impact on subsequent conditioning, preexposure in the presence of the shock retarded both excitatory and inhibitory conditioning. We conclude that the introduction of the US during the conditioning phase of a normal LI experiment can produce a contextual change that reduces the observed magnitude of LI.

Conditioned Suppression and the Effects of Pentobarbital with Picrotoxin, Flumazenil, and R05-3663

In two experiments, rats trained to lever press for food were maintained under a conditioned suppression procedure and then given an acute regime of drug administration involving pentobarbital (10 mg/kg). In both experiments, pentobarbital reduced conditioned suppression. In the first experiment (4 rats), this effect was increased by the combination of the specific benzodiazepine antagonist flumazenil (10 mg/kg) with pentobarbital but unaffected by the combination of picrotoxin (1.5 mg/kg) with pentobarbital. In the second experiment (3 rats), this effect was attenuated when picrotoxin (2.0 mg/kg) or Ro5-3663 (5.0 mg/kg) were also administered. These findings add to the data on the effects of anxiolytics and related compounds on conditioned suppression, they provide more information on the possible nature of the GABA/benzodiazepine receptor complex and suggest that flumazenil can have anxiolytic as well as anxiogenic effects.

5,7-Dihydroxytryptamine lesions in the fornix—fimbria attenuate latent inhibition

When animals are preexposed to a stimulus without consequence they are subsequently slower to associate this stimulus with an important event, such as footshock. This retarding effect of stimulus preexposure is called latent inhibition and can be demonstrated in a variety of classical and instrumental paradigms and in a wide range of species, including man. Latent inhibition is disrupted in acute schizophrenics and by amphetamine treatment in both rat and man. The present study investigated the role of hippocampal 5HT terminals in latent inhibition using a conditioned suppression procedure with male Sprague-Dawley rats. Microinjections of 5,7-dihydroxytryptamine in the fornix-fimbria significantly reduced hippocampal indoleamine levels and attenuated latent inhibition of conditioned suppression. This finding supports the hypothesis that the destruction of mesolimbic 5-hydroxytryptamine terminals reduces latent inhibition. This result is discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder. In addition to the predicted lesion effect, biochemical analyses indicated that experimental treatments in the latent inhibition procedure altered neurotransmitter turnover: utilization ratios for 5-hydroxytryptamine and/or dopamine were increased in preexposed relative to nonpreexposed animals in four of the six brain regions sampled.