Pavlovian second-order conditioned analgesia

Three experiments with rat subjects assessed conditioned analgesia in a Pavlovian second-order conditioning procedure by using inhibition of responding to thermal stimulation as an index of pain sensitivity. In Experiment 1, rats receiving second-order conditioning showed longer response latencies during a test of pain sensitivity in the presence of the second-order conditioned stimulus (CS) than rats receiving appropriate control procedures. Experiment 2 found that extinction of the first-order CS had no effect on established second-order conditioned analgesia. Experiment 3 evaluated the effects of post second-order conditioning pairings of morphine and the shock unconditioned stimulus (US). Rats receiving paired morphine-shock presentations showed significantly shorter response latencies during a hot-plate test of pain sensitivity in the presence of the second-order CS than did groups of rats receiving various control procedures; second-order analgesia was attenuated. These data extend the associative account of conditioned analgesia to second-order conditioning situations and are discussed in terms of the mediation of both first- and second-order analgesia by an association between the CS and a representation or expectancy of the US, which may directly activate endogenous pain inhibition systems.     

Blocking with serial compound stimuli: The role of local context and second-order associations

Blocking was studied with rats in two serial conditioning experiments in which CS1 was followed by CS2 and then shock. Experiment 1 demonstrated that pretraining with CS1 was able to block conditioning to CS2 when the pretraining consisted of trace conditioning. But when serial conditioning was used for pretraining, with a third stimulus as the second element of the compound, then blocking was not detected during the subsequent phase. In Experiment 2 the effect of pretraining with CS2 on blocking with CS1 was examined. Blocking was effective, but only when steps were taken to minimize the growth of second-order associations resulting from the pairing of CS1 with CS2. These results are consistent with a principle stating that the ability of a pretrained stimulus to block the added stimulus in a compound depends on the relative contiguity of each stimulus to the US.     

Locus of the effect of a surprising reinforcer in the attenuation of blocking

Previous experiments on conditioned suppression in rats have shown that prior conditioning to one element of a compound conditioned stimulus paired with shock may block or prevent conditioning to the other element. Reliable conditioning may, however, occur to the added element (blocking may be attenuated), if a surprising second shock is added shortly after each compound trial. Experiment I confirmed this finding, and further showed that blocking was attenuated only when the second shock occurred 10 s after the compound trial, not when it occurred 100 s later. Experiment II showed that the surprising omission of an expected second shock 10 s after each compound trial would also attenuate blocking, thus implying that the surprising event does not itself act to reinforce conditioning to the added element, but rather permits the unconditioned stimulus (the first shock) to play its normal role as an effective reinforcer. This conclusion was confirmed by Experiment III, which showed that a surprising second shock does not produce any increase in conditioning to the added element on the trial on which it occurs; rather it serves to ensure adequate conditioning to that element on a subsequent compound trial. The implication is that the surprising event acts proactively to prevent subjects learning to ignore an otherwise redundant stimulus.     

Conditioned inhibition of fear: Evidence for a competing response mechanism

In two experiments, inhibitory conditioning was attempted by presenting a discrete CS in a neutral stimulus environment shortly following the termination of either shock (Experiment 1) or a second discrete CS which had been paired in a forward manner with shock (Experiment 2). Evidence of successful inhibitory conditioning was mixed in Experiment 1, where the properties of the CS were assessed within an escape-from-fear procedure. Postresponse presentations of the CS enhanced performance, whereas the presentation of the CS prior to responding did not have the expected degrading effect on performance. In Experiment 2, the inhibitory properties of the CS were assessed by combining this stimulus with an excitatory CS and presenting the compound to rats engaged in a water-reinforced licking response. Less response suppression was found in reaction to this compound relative to three separate comparison conditions, thus witnessing the success of the inhibitory-conditioning procedure used. The common assumption that inhibitory conditioning results from the nonreinforcement of a CS in a situation where reinforcement is expected, i.e., one which contains previously reinforced cues, is not supported by these data, for no previously reinforced cues were simultaneously presented with the CS during inhibitory training. The data are in agreement with a conditioned antagonistic-response interpretation of inhibitory conditioning.     

Effect of posttrial episodes on conditioning in compound conditioned stimuli

The effect of signaled and nonsignaled posttrial episodes (PTEs) on conditioning to the target CS of a preceding compound CS-US trial was examined in two conditioned emotional response (CER) experiments with rats. Experiment 1 revealed that a nonsignaled PTE, a second shock US, interfered with conditioning to the preceding target CS and that the interference effect of the PTE was greater when it occurred 5 sec as opposed to 1,800 sec after the preceding compound CS-US trial. Experiment 2 revealed that if the shock PTE was signaled by a CS, its ability to interfere with conditioning was reduced. This second study also revealed that omission of an "expected" US interfered with conditioning to the target CS. The implications of these data for information processing models of Pavlovian conditioning are discussed.     

Preexposure to the CS alone,US alone,or CS and US uncorrelated: Latent inhibition,blocking by context or learned irrelevance?

Three experiments on conditioned suppression in rats examined the extent to which preexposure to the CS, the US, or uncorrelated presentations of both interfere with future conditioning. Experiment 1 suggested that the interference caused by preexposure to the US alone may result from blocking by contextual cues: signaling the US during preexposure attenuated the interference. Experiment 2 demonstrated that signaling the US by another stimulus did not attenuate the interference caused by exposure to uncorrelated presentations of CS and US. Experiment 3 replicated the results of Experiments 1 and 2 and directly compared the magnitude of these deficits. The results of these experiments imply that the effects of exposure to uncorrelated presentations of CS and US are not reducible to the sum of the effects of exposure to CS or US alone.     

Associative changes with a random CS-US relationship

Three experiments examined conditioned magazine approach in rats when a positive unconditioned stimulus (US) bore a random relation to a conditioned stimulus (CS). Experiment 1 found that over the course of conditioning the CS initially elevated responding relative to the baseline but then lost the power to do so. Transfer tests revealed that a CS-US association developed early and persisted despite the decline in magazine responding. Experiment 2 confirmed the persistence of CS-US associations and found them to be more substantial when a different US occurred during the CS than in its absence. In Experiment 3, when the situation was exposed to US-alone presentations prior to introducing the CS, there was little evidence that a subsequent random relation between the CS and US produced an association between them. These results agree with those of blocking and overshadowing experiments using discrete CSs and support an interpretation of the random procedure in terms of competition between the background and CS for conditioning.     

Blocking as a retrieval failure: Reactivation of associations to a blocked stimulus

Conditioned lick suppression in rats was used to examine the effectiveness of three different “reminder” treatments in reactivating associations to a blocked stimulus in a Kamin blocking paradigm. Experiment I indicated that with our parameters prior tone-footshock pairings could block manifestation of a light-footshock association that would otherwise be evident following pairings of a light-tone compound stimulus with footshock. In Experiment II, exposure to either the US, the blocked stimulus (light), or the apparatus cues between the compound conditioning trials and testing decreased blocking. Experiments III(a) and III(b) replicated the unblocking effects seen in Experiment II and included control groups that received the identical training and reminder treatments except for the omission of the light from the compound stimulus. These latter animals failed to display behaviour comparable to the blocked and reminded subjects, thereby establishing the associative basis of suppression to the light in the animals reminded following treatment known to produce blocking. Experiment IV also replicated the results of Experiment II and included control groups that received identical light-tone compound trials and reminder treatments without prior conditioning to the tone alone. In these control groups, reminder treatments tended to disrupt rather than increase evidence of conditioning to the light. The results suggest that associations are formed to the added element of a compound despite prior conditioning to the initial element, and that failure on the test trial to retrieve these associations to the blocked CS, rather than a failure to attend to or learn about the added element, is at least in part responsible the Kamin blocking effect.     

Malleability of conditioned associations: path dependence

Using conditioned suppression of barpressing to investigate the stability of a conditioned stimulus-unconditioned stimulus (CS-US) association, we gave water-deprived rats either a few pairings of the CS with a strong footshock US or many pairings with a weak footshock US so that barpress suppression in response to the CS was equated. Experiment 1 established training parameters that yielded this equivalence. Specifically, rapid acquisition to a preasymptotic level of responding with strong shock produced suppression comparable to the asymptotic level reached more slowly with weak shock. Experiment 2 showed that although equivalent performance was obtained from extensive conditioning with a weak shock or limited conditioning with strong shock, only extensive conditioning with weak shock resulted in retarded acquisition of an association between that same CS and a footshock level perceived as midway between the two initial training shock intensities as implied by asymptotic performance in Experiment 1. Experiment 3 demonstrated that the observed retardation in animals given many conditioning trials with weak shock was CS specific. Collectively, these findings indicate that the malleability of learned behavior is not simply a function of initial associative strength but is dependent on path during initial acquisition.     

The Influence of Retention Interval on the US Preexposure Effect: Changes in Contextual Blocking over Time

A number of studies manipulating the length of the interval between conditioning and testing indicate spontaneous recovery from overshadowing, suggesting that certain instances of overshadowing represent a deficit in memory retrieval rather than a failure of animals to form an association between the overshadowed stimulus and the US. The present series of experiments examined the influence of lengthening the retention interval on blocking, another stimulus selection phenomenon that is typically interpreted as an acquisition deficit. The results indicated that when subjects were tested shortly (3 days) after training conditioning to a taste blocked subsequent conditioning to an odor conditioned in compound with that taste (Experiment 1), whereas prior conditioning to an odor did not block subsequent conditioning to a taste conditioned in compound with that odor (Experiment 2). This pattern of results was essentially unchanged when testing occurred at a longer (21-day) retention interval. However, there was evidence of a US preexposure effect in Experiment 2 when subjects in the US ONLY control condition were tested at the 3-day retention interval, but not when testing occurred 21 days after conditioning. Experiments 3 and 4 examined whether this loss of the US preexposure effect over time might actually represent a change in the degree of contextual blocking as the retention interval is lengthened. Exposure to the conditioning context either during the interval between Phase 1 and Phase 2 of conditioning (Experiment 3) or prior to Phase 1 of conditioning (Experiment 4) alleviated this US preexposure effect suggesting that the loss of the US preexposure effect as the retention interval is lengthened observed in Experiment 2 is due to changes in the degree of blocking by contextual stimuli over time. The results are discussed in terms of differential susceptibility of forgetting of two functional roles played by a contextual stimuli in the current situation-context as a CS and context as a retrieval cue for other CS-US associations.     

Changes in pain reactivity induced by unconditioned and conditioned excitatory and inhibitory stimuli

In three experiments we investigated the effects of aversive-conditioning components on the reactivity of rats to pain. After training in Experiment 1 with a discrete conditioned stimulus (CS) for a shock unconditioned stimulus (US), different groups were exposed to the CS, US, CS/Us compound, just the training context, or none of those immediately prior to a hot-plate test assessing the latency of a paw-lick response. Relative to no exposure and context alone, the CS produced a shorter latency--that is, an apparent sensitization effect--whereas the US produced a longer latency--that is, a hypoalgesic effect--that was actually augmented by the CS/US compound. Furthermore, whereas the US-induced hypoalgesia was unaffected by the opiate antagonist, naloxone, hypoalgesia produced by the CS/US compound was appreciably decremented by the drug. Experiment 2 showed the same effects with parameters more typical of conditioning research. Experiment 3 compared signals for the presence (CS+) and absence (CS-) of the US. The CS- did not itself affect pain reactivity, but in inhibited the effects of the CS+, US, and CS+/US compound. Collectively, the results suggest that a CS+sensitizes the animal to imminent events and also potentiates an opioid reaction that supplants the less effective nonopioid hypoalgesia induced by the US. In contrast, a CS- functions as a general moderator of excitation, inhibiting both sensitization and hypoalgesic effects, whether opioid or nonopioid.     

Mechanisms underlying retarded emergence of conditioned responding following inhibitory training: evidence for the comparator hypothesis

The comparator hypothesis posits that conditioned responding is determined by a comparison at the time of testing between the associative strengths of the conditioned stimulus (CS) and stimuli proximal to the CS at the time of conditioning. The hypothesis treats all associations as being excitatory and treats conditioned inhibition as the behavioral consequence of a CS that is less excitatory than its comparator stimuli. Conditioned lick suppression by rats was used to differentiate four possible sources of retarded responding to an inhibitory CS. These include habituation to the unconditioned stimulus (US), latent inhibition to the CS, blocking of the CS-US association by the conditioning context, and enhanced excitatory associations to the comparator stimuli. Prior research has demonstrated the first three phenomena. Therefore, we employed parameters expected to highlight the fourth one--the comparator process. In Experiment 1, our negative contingency training was shown to produce a conditioned inhibitor that passed inhibitory summation and retardation tests. In Experiment 2 we found transfer of retardation from an inhibitory CS to a novel stimulus when the location where retardation-test training occurred was excitatory, which is indicative of contextual blocking and/or comparator effects. In Experiment 3, extinction of the conditioning context was found to attenuate retardation regardless of whether extinction occurred before or after the CS-US pairings of the retardation test. This indicates that much of the present retardation was due to the comparator process rather than to contextual blocking. Experiment 4 demonstrated that habituation to the US did not contribute to retardation in the present case. Collectively, these studies suggest that retardation following inhibitory training can be explained without recourse to any of the traditional mechanisms of conditioned inhibition.     

Compound conditioning: Elimination of the blocking effect

Prior conditioning employing one element of a compound stimulus as the CS blocked the acquisition of a Conditioned Emotional Response (CER) to the second element of a simultaneous compound stimulus that was subsequently used as the CS in further conditioning trials. Presentation of a brief “surprise” stimulus 3 or 5 sec after the occurrence of the US during the compound trials eliminated the blocking effect.     

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.     

Overshadowing of subsequent events and recovery thereafter

Four experiments using a conditioned lick suppression preparation with rats were conducted to examine whether overshadowing of subsequent events could be obtained in Pavlovian backward conditioning (i.e. unconditioned stimulus [US] before conditioned stimulus [CS]), and to determine whether such overshadowing could be reversed without further training with the overshadowed CS, as has been reported in overshadowing of antecedent events. In Experiment 1, a backward-conditioned CS overshadowed a second backward-conditioned CS. Two posttraining manipulations, extinction of the overshadowing CS (Experiment 2) and shifting of the temporal relationship of the overshadowing CS to the US (Experiment 3), increased responding to the overshadowed CS. These results constitute the first unambiguous demonstration of stimulus competition between subsequent events using first-order conditioning, and they show that, like overshadowing with forward conditioning, such overshadowing is due, at least in part if not completely, to a failure to express information that had been acquired.     

Conditioned taste aversion is enhanced when the unconditioned stimulus is presented in a different context

Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D) showed a more marked conditioned aversion to the CS than animals which were given both the CS and the US in the same context (Group S). Experiment 2 found that in both Group D and Group S, aversion to the CS increased when the subjects were exposed to the conditioned context after the conditioning. These findings supported the argument that the strength of the CS-US association acquired during conditioning is compared with that of the context-US to determine the magnitude of aversion revealed to the CS.     

Mechanisms of blocking by contextual stimuli

The influence of contextual stimuli on the conditioning and performance of responding to a discrete stimulus was examined in the US preexposure paradigm using both context shift manipulations and a measure of context conditioning. Four groups of rats received both repeated exposure to an electric shock US in one context (Context 1), and repeated nonshocked exposure to a second context (Context 2). Two additional groups of rats received exposure to these contexts, but never received shock presentations. Rats exposed to shock learned to escape from the stimuli of Context 1, but did not escape from the stimuli provided by Context 2. Rats not exposed to shock failed to escape from either context. All rats then received a single CER conditioning session in which four pairings of a 3-min noise CS and shock US were presented. Half the rats received those CS-US pairings in the excitatory Context 1, while the remaining rats received those pairings in the neutral Context 2. Finally, half the rats in each of the CER conditioning treatments received extinction test trials of the noise CS in Context 1, while the remaining rats received those test trials in Context 2. Thus, this design factorially manipulated the presence of excitatory or neutral contextual stimuli during both conditioning and testing of a discrete CS. In comparison with the two groups of rats never preexposed to shock alone, attenuation in acquisition of conditioned suppression observed during test trials occurred only when CER conditioning had been administered in the excitatory Context 1, and this effect was manifested when testing occurred in either the excitatory Context 1 or the neutral Context 2. These results support the model of R. A. Rescorla and A. R. Wagner (1972) (in A. H. Black & W. F. Prokasy (Eds.) Classical Conditioning II, pp. 64–99, New York: Appleton-Century-Crofts) which asserts that contextual stimuli and sicrete CSs compete for limited associative strength supportable by a given US.     

Opioid receptors mediate direct predictive fear learning: evidence from one-trial blocking

Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including μ-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective μ-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.     

Medial auditory thalamic input to the lateral pontine nuclei is necessary for auditory eyeblink conditioning

Auditory and visual conditioned stimulus (CS) pathways for eyeblink conditioning were investigated with reversible inactivation of the medial (MPN) or lateral (LPN) pontine nuclei. In Experiment 1, Long-Evans rats were given three phases of eyeblink conditioning. Phase 1 consisted of three training sessions with electrical stimulation of the medial auditory thalamic nuclei (MATN) paired with a periorbital shock unconditioned stimulus (US). An additional session was given with a muscimol (0.5 μL, 10 mM) or saline infusion targeting the LPN followed by a recovery session with no infusions. The same training and testing sequence was then repeated with either a tone or light CS in phases 2 and 3 (counterbalanced). Experiment 2 consisted of the same training as Experiment 1 except that muscimol or saline was infused in the MPN during the retention tests. Muscimol infusions targeting the LPN severely impaired retention of eyeblink conditioned responses (CRs) to the MATN stimulation and tone CSs but only partially reduced CR percentage to the light CS. Muscimol infusions that targeted the MPN had a larger effect on CR retention to the light CS relative to MATN stimulation or tone CSs. The results provide evidence that the auditory CS pathway necessary for delay eyeblink conditioning includes the MATN-LPN projection and the visual CS pathway includes the MPN.     

Blocking of conditioning of tentacle lowering in the snail (Helix aspersa)

Experiment 1 established the effectiveness of an appetitive conditioning of odours procedure with snails (Helix aspersa) that was subsequently used for the study of blocking. In this important phenomenon, the conditioning of a CS1 (where CS is the conditioned stimulus) prior to conditioning of a compound, CS1CS2, blocked the conditioning to the CS2. Experiments 2a, 2b, and 2c demonstrated this associative effect using three different experimental controls. Experiments 3a and 3b replicated the blocking effect and allowed us to reject an explanation of blocking based on generalized effects of several treatments of diverse stimuli in blocking and control groups (the pseudoblocking effect). The implications of these results for the study of invertebrate cognition by means of conditioning techniques are discussed.