Conditioned Suppression Task Research Articles

Compulsive-like eating of high-fat high-sugar food is associated with 'addiction-like' glutamatergic dysfunction in obesity prone rats.

Chronic overeating is a core feature of diet‐induced obesity. There is increasing evidence that in vulnerable individuals, such overeating could become compulsive, resembling an addictive disorder. The transition to compulsive substance use has been linked with changes at glutamatergic synapses in the nucleus accumbens. In this study, we investigated a potential link between such glutamatergic dysregulation and compulsive‐like eating using a rat model of diet‐induced obesity. A conditioned suppression task demonstrated that diet‐induced obese rats display eating despite negative consequences, as their consumption was insensitive to an aversive cue. Moreover, nucleus accumbens expression of GluA1 and xCT proteins was upregulated in diet‐induced obese animals. Lastly, both a computed ‘addiction score’ (based on performance across three criteria) and weight gain were positively correlated with changes in GluA1 and xCT expression in the nucleus accumbens. These data demonstrate that the propensity for diet‐induced obesity is associated with compulsive‐like eating of highly palatable food and is accompanied by ‘addiction‐like’ glutamatergic dysregulation in the nucleus accumbens, thus providing neurobiological evidence of addiction‐like pathology in this model of obesity.

Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization.

Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.

Acquired equivalence and generalized suppression in a virtual reality environment

Acquired equivalence was investigated using a virtual reality conditioned suppression task administered in a first-person-shooter game. Two visual cues, A1 and B1, were followed by a tone (O1), and another two cues, A2 and B2, were followed by another tone (O2). During differential Pavlovian conditioning, A1 was paired with an instructed unconditioned stimulus (US) consisting of a flashing white screen, whereas A2 was not. All cues and outcomes were then presented at test, in the absence of the US, and suppression ratios were calculated for multiple response topographies (shots, hits, and breaks). Clear evidence of the suppression of shots was seen for A1 and B1, with no suppression being seen for either A2 or B2. Presentations of O1 and O2 resulted in significant suppression of shots and hits, whereas only O1 led to the suppression of breaks. The US expectancy ratings were consistent with these behavioral results. The findings are discussed in the light of differing accounts of acquired equivalence.

Adolescent traumatic stress experience shapes adulthood fear conditioning and extinction responses

A traumatic stress paradigm (underwater trauma, UWT) was used to model an intense developmental stress event during adolescence, and evaluate effects on fear and stress response lasting into adulthood. Adolescent rats (P37) were exposed to UWT or swim without submersion. Rats were then allowed to reach adulthood (P114) and fear conditioned using light and sound (conditioned stimulus), with or without footshock (unconditioned stimulus). After a three‐week fear incubation period, rats were given one extinction trial per day for five consecutive days using an operant behavior conditioned suppression task. Preliminary results suggest that adolescent traumatic stress experience shapes some aspects of adulthood stress response severity, and residual fear responses after five extinction trials.This work is supported by the Military Operational Medicine Research Program, US Army Medical Research and Materiel Command.

Unpredictability and Context Conditioning: Does the Nature of the US Matter?

Using a conditioned suppression task, we examined the minimal conditions to establish context conditioning as induced by unpredictability of an unconditioned stimulus (US). We investigated whether a biologically significant US is necessary to produce such context conditioning effects. In this between-subjects experiment, we manipulated the nature of the US and US-unpredictability. In the Paired condition, the conditioned stimulus (CS) was always followed by the US, whereas in the Unpaired condition, the CS and the US were presented explicitly unpaired, that is, the CS was never followed by the US. Half of the participants received an aversive, biologically significant human scream, and the other half received a more neutral, biologically non-significant sound as US. Results show more contextual suppression in the Unpaired condition than in the Paired condition. We conclude that in an expectancy-based conditioning task, US-unpredictability, but not a biologically potent US, is crucial to establish context conditioning.

The temporal pattern of responding in conditioned bar-press suppression: The role of the context switch and training mode

The present study examined the temporal pattern of responding in a conditioned bar-press suppression task in rats. Rats were exposed to either a 30-s or a 120-s conditioned stimulus (CS) followed by a footshock. Training took place either while the rats were lever-pressing for water (online), or with the lever removed from the box (offline). They were then exposed to the CS while they were lever-pressing for water, either in the training context or in a different context. Bar-press suppression during the CS was constant across the duration of the CS during training, but was restricted to the initial portion of the CS at the time of testing, especially when subjects were tested in a different context. Those results replicate the reactive (as opposed to anticipatory) pattern observed in a lick suppression procedure by Jozefowiez et al. (2011) and indicate that a change in context at the time of testing might be critical for its expression.

The effects of acoustic trauma that can cause tinnitus on spatial performance in rats

Previous studies have shown that acoustic trauma can disrupt the firing of place cells in the hippocampus and also inhibit hippocampal neurogenesis, suggesting that such trauma might impair spatial memory. In this study, we investigated performance in the alternating T maze and Morris water maze of rats exposed to acoustic trauma (16 kHz, 110 dB SPL pure tone for 1 h), who had elevated auditory brainstem response thresholds and the psychophysical attributes of tinnitus (using a conditioned lick suppression task). To our surprise, we found that rats with tinnitus did not perform significantly differently from sham control animals in either the alternating T maze task or any aspect of the reference or working memory versions of the Morris water maze task except for a faster acquisition in T maze alternation. These results suggest that acoustic trauma and tinnitus may not impair spatial memory in rats.

The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats

Previous studies in animals and humans have shown that, in some cases at least, anti-epileptic drugs can reduce the severity of tinnitus. Given that cannabinoid receptor agonists have been shown to exert anti-epileptic effects in some circumstances, we investigated whether two synthetic CB 1/CB 2 receptor agonists, WIN55,212-2, and CP55,940, could inhibit the behavioural manifestations of salicylate-induced tinnitus in rats in a conditioned suppression task. We found that neither WIN55,212-2 (3.0 mg/kg s.c) nor CP55,940 (0.1 or 0.3 mg/kg s.c), significantly reduced conditioned behaviour associated with tinnitus. However, both 3 mg/kg WIN55,212-2 and 0.3 mg/kg CP55,940 did significantly increase tinnitus-related behaviour compared to the vehicle control groups. These results suggest that cannabinoid receptor agonists may not be useful in the treatment of salicylate-induced tinnitus and that at certain doses, they could actually exacerbate the condition.

Retrospective revaluation effects following serial compound training and target extinction

Using a conditioned suppression task, two experiments examined retrospective revaluation effects after serial compound training in a release from overshadowing design. In Experiment 1, serial X → A+ training produced suppression to target A, which was enhanced when preceded by feature X, whereas X by itself elicited no suppression. Subsequent A− presentations extinguished responding to A, but had no effect on either responding to X → A or X alone. However, the addition of A− trials did enhance the ability of feature X to elicit suppression to a novel target, B, suggesting retrospective revaluation of X’s properties. Experiment 2 showed that the enhanced transfer effect, observed in Experiment 1, was independent of the training history of the target (B− or Y → B+/B−). Together, these results suggest that feature X did not retrospectively acquire excitatory strength or occasion setting power, but rather a generalized ability to increase responding to any other cue.

The effects of context changes on the reinstatement of extinguished conditioned behavior in a conditioned suppression task with humans

Reinstatement refers to the return of previously extinguished conditioned responses to test trials of a conditional stimulus (CS) when presentations of the unconditional stimulus (US) alone are given following extinction. Four experiments were conducted to determine whether reinstatement could be found in a conditioned suppression task with humans and whether contextual changes can abolish it. Experiment 1 demonstrated the reinstatement of conditioned suppression when acquisition, extinction, US alone, and test trials were all given in the same context. Experiments 2 and 3 suggested that the reinstatement effect was still present when the US alone presentations were given in a different context to the subsequent test trials. Experiment 4 replicated this effect using additional controls over the amount of exposure to the various contexts. The results suggest that reinstatement can be robust across changing contexts. Aspects of the conditioned suppression task that promote the transfer of learning across contexts or the establishment of configural context-CS stimuli may underlie the apparent lack of contextual control over reinstatement.

The resistance of renewal to instructions that devalue the role of contextual cues in a conditioned suppression task with humans

The renewal of extinguished conditioned behaviour appears to reflect context-dependent learning. The present research used a conditioned suppression task with humans to examine whether instructions concerning the context could influence renewal. Pairings of a conditional stimulus (CS) and unconditional stimulus (US) were made in one context, followed by extinction trials of CS alone in a second context, and test trials of CS alone upon return to the original learning context. Four experiments tested whether the renewal of conditioned suppression observed during test would be attenuated if participants were instructed that the context changes were irrelevant to the predictive relationship between the CS and US. Using a differential conditioning design, no attenuation was found when the instructions were given prior to conditioning (Experiment 1) or immediately prior to the test trials (Experiment 2). The latter result was replicated with a single-cue conditioning design and further controls for exposure to the extinction contexts (Experiment 3). The collection of on-line ratings about the relationship between the contextual changes and the predictive nature of the CS indicated that participants did attend to and believe the instructions (Experiment 4). The results point to the resistance of renewal to explicit instructions that attempt to devalue the role of the contextual cues.

The effects of physical context changes and multiple extinction contexts on two forms of renewal in a conditioned suppression task with humans

Three experiments examined the effects of physical context changes and multiple extinction contexts on the renewal of conditioned suppression in humans. A conditioned suppression task used an undesirable event as the unconditional stimulus (US). One conditional stimulus (CS+) predicted the occurrence of the US and another (CS−) predicted US absence. In Experiment 1 ( N = 32), conditioned suppression was acquired to the CS+ in one context and extinguished in a different context. An increase in suppression was found for the CS+ and not for the CS− when subsequent test trials were conducted in the acquisition context (ABA renewal). Experiment 2 ( N = 32) tested for ABC Renewal and showed increased suppression to both the CS+ and CS− when test was conducted in a novel context. Experiment 3 ( N = 80) showed that these two effects were abolished when extinction was conducted in multiple contexts. The experiments extend the ABA renewal of conditioned suppression found with non-human animal subjects and the reduction of renewal by extinction in multiple contexts. Context changes may also facilitate cue competition effects after training with elementary stimuli, as shown by the effects of US omission in the ABA and ABC renewal groups.

Extinction and renewal of Pavlovian modulation in human sequential Feature Positive discrimination learning

Using a conditioned suppression task, we investigated extinction and renewal of Pavlovian modulation in human sequential Feature Positive (FP) discrimination learning. In Experiment 1, in context a participants were first trained on two FP discriminations, X-->A+/A- and Y-->B+/B-. Extinction treatment was administered in the acquisition context a (aaa group) or in a new context b (aba group), and comprised X-->A- extinction and Y- control trials. Discriminative X-->A/A responding was lost in both groups when tested in the extinction context, but partially recovered in the aba and not in the aaa group when tested in the acquisition context, suggesting extinction and renewal of extinguished modulation. The same was observed for the Y-->B/B control pair, however, questioning whether the loss of discriminative X-->A/A responding represented genuine extinction of modulation. In Experiment 2, including only aba groups, participants were trained in context a on two FP discriminations, X-->A+/A- and Y-->B+/B-, after which the group "Extinction" was exposed to X-->A- extinction trials in context b, whereas the group "Control" was exposed to X- control trials; concurrently, both groups received further Y-->B+/B- training. In the group Control, differential Y-->B/B and X-->A/A responding were acquired and maintained throughout the experiment. In the group Extinction, while Y-->B/B responding was also maintained throughout, differential X-->A/A responding disappeared because of X-->A- extinction treatment when tested in the extinction context b, but partially reappeared when tested in the acquisition context a. This evidences aba-renewal of extinguished modulation.

Thwarting the renewal (relapse) of conditioned fear with the explicitly unpaired procedure: Possible interpretations and implications for treating human fears and phobias

In three experiments using the barpress conditioned suppression task with albino rats, we studied the renewal (relapse) of conditioned fear in an ABA fear-renewal paradigm. We found that explicitly unpaired (EU) deliveries of conditioned stimuli (CSs) and unconditioned stimuli (USs) in Context B thwarted fear renewal in Context A. Evidence contraindicated a suggestion by Rauhut, Thomas, and Ayres (2001) that US habituation plays a key role in this effect. For example, renewal was thwarted only when EU CSs and USs were intermingled rather than given in succession. The possibility that EU treatments thwart renewal by creating a CS that inhibits fear in the test context also received no support. Thus, summation and retardation tests in Context A found no evidence that the EU CS became inhibitory, finding instead evidence for a residual excitation. Other possible interpretations of the results and some implications for clinical practice are noted.

Simultaneous and sequential Feature Negative discriminations: Elemental learning and occasion setting in human Pavlovian conditioning

Using a conditioned suppression task, we investigated simultaneous (XA−/A+) vs. sequential (X → A−/A+) Feature Negative (FN) discrimination learning in humans. We expected the simultaneous discrimination to result in X (or alternatively the XA configuration) becoming an inhibitor acting directly on the US, and the sequential discrimination in X becoming a negative occasion setter acting indirectly on the A–US link. After simultaneous FN training, X+ training completely abolished discriminative XA/A responding (Experiment 1), and X transferred inhibition to new targets B regardless of their training history (B+ or YB−/B+) (Experiment 2), suggesting X became a simple inhibitor. After sequential FN training, X showed the predicted selective transfer to a target B that also had been modulated (Y → B−/B+), not to a simple excitor (B+) (Experiment 4), but turning X into an excitor (X+) likewise disrupted discriminative X → A/A responding (Experiment 3). This suggests that X acquired a combination of modulatory and direct inhibitory properties, and that the joint contribution of both components is necessary for the suppression of the target-induced US activation.

Cross-modal neuroplasticity in neonatally enucleated hamsters: structure, electrophysiology and behaviour.

Potential auditory compensation in neonatally bilaterally enucleated Syrian hamsters was explored anatomically, electrophysiologically and behaviourally. Gross morphology of the visual cortex appeared normal and no obvious cytoarchitectural malformation was discerned. However, enucleation induced a significant increase in the spontaneous firing rate of visual cortex cells. Further, auditory stimuli elicited field potentials and single unit responses in the visual cortex of enucleated, but not normal, animals. About 63% of the cells isolated in the visual cortex of 16 enucleated hamsters responded to at least one type of auditory stimulus. Most of the responses were less vigorous and less time-locked than those of auditory cortex cells, and thresholds were typically higher. Projection tracing with WGA-HRP disclosed reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus in both intact and enucleated animals. However, in the enucleated animals retrogradely labelled cells were also found in the inferior colliculus, the major midbrain auditory nucleus. Behaviourally determined auditory sensitivity across the hearing range did not differ between enucleated and intact hamsters. Minimum audible angle, as determined by a conditioned suppression task, ranged from around 17 to 22 degrees, with no significant difference between normal and enucleated animals. The two groups also did not differ with regard to the direction of their unconditioned head orientating response to intermittent noise. However, the enucleated animals showed a more vigorous response and were slower to habituate to the noise. These results show that bilateral enucleation of newborn hamsters results in auditory activation of visual targets, in addition to the typical activation of the intact auditory pathway. Behaviourally it appears that enucleated hamsters, compared with their normal littermates, are slower to habituate in their response to an unexpected source of sound.

Evidence for Learning-Deficit versus Performance-Deficit Theories of Latent Inhibition in Pavlovian Fear Conditioning

In a conditioned suppression task with rats, we used retention-interval and context-switch maneuvers in an effort to affect retrieval of interfering associations often held responsible for the effects of preexposing conditioned stimuli (CSs). In Experiment 1, we found that preexposing CS A reduced its subsequent ability to support second-order conditioning to CS X. Inserting a 28-day retention interval between A+ and X → A (second-order conditioning) phases did not restore that ability. It did, however, increase A's ability to acquire conditioned suppression during the second-order phase, suggesting renewed attention to A. In Experiment 2, we found that preexposing CS A reduced its ability to serve later as a blocker. Conducting the blocking test outside the preexposure context did not restore that ability, but conducting the element training phase outside the preexposure context did. Results favor learning-deficit theory over a retrieval-interference version of performance-deficit theory of CS-preexposure effects.

The effects of hippocampal aspiration lesions on conditioning to the CS and to a background stimulus in trace conditioned suppression

Rats with hippocampal aspiration lesions or cortical control lesions were compared to sham operated controls in a trace conditioned suppression task, in which a long-lasting background stimulus played the role of more conventional contextual cues. In all three surgical treatment groups, conditioning to the explicit conditioned stimulus (CS) decreased, but conditioning to the background cue increased, when a longer trace interval was used. There was thus no evidence of a differential partitioning of associative conditioning as a result of the lesion, despite the evident sensitivity of the behavioural paradigm to variations in the CS→unconditioned stimulus (US) interval. This result contrasts with earlier reports using conventional contextual cues in analogous experimental designs, and so suggests that the sensitivity of contextual conditioning to hippocampal dysfunction depends at least in part on the physical nature of conventional contextual cues, and not solely on the less precise predictive information that such cues typically provide.

Retinal transplant-mediated learning in a conditioned suppression task in rats.

Retinae were transplanted from embryonic rats to a location over the midbrain of unilaterally anucleated newborn rats. At maturity, the rats were trained to "lever-press" for a food reward. By using a Pavlovian conditioned suppression paradigm, it was found that light delivered to the transplant could be recognized by the host rat as a conditioned stimulus, resulting in a reduced rate of lever pressing.

GABAergic modulation of memory with regard to passive avoidance and conditioned suppression task in mice.

The role of GABAergic neuronal system in learning and memory was investigated using the step-down typed passive avoidance and rapidly learned conditioned suppression tasks in mice. GABA antagonists, picrotoxin and bicuculline, or a GABA synthesis inhibitor, 3-mercaptopropionic acid (3-MP), were administered just after the training test. All of these drugs caused amnesia: they shortened the step-down latency (SDL) and attenuated the conditioned suppression of motility in the retention test conducted 24 h after the administration. Furthermore, we investigated the effect of GABA receptor agonists, muscimol and baclofen, or a GABA transaminase inhibitor, aminooxyacetic acid (AOAA), on these amnesia models. GABA agonists showed an antiamnesic action as follows: in the passive avoidance task, 1) picrotoxin-induced amnesia was antagonized by muscimol, baclofen and AOAA. 2) Bicuculline-induced amnesia was antagonized by muscimol and AOAA but not by baclofen. 3) 3-MP-induced amnesia was antagonized only by muscimol. 4) In the rapidly learned conditioned suppression task, picrotoxin-, bicuculline- and 3-MP-induced amnesia were antagonized by muscimol, baclofen and AOAA. These results suggest that the GABAergic neuronal system plays an important role in the memory retention of passive avoidance and rapidly learned conditioned suppression tasks.