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.     

Classical conditioning of the nictitating membrane response of the lemon shark (Negaprion brevirostris)

An experimental group of lemon sharks received 100 daily presentations of light flash as the conditioned stimulus (CS) and electric shock as the unconditioned stimulus (US) in a classical conditioning situation. The conditioned responses (CRs) and unconditioned responses (URs) under observation consisted of extensions of the nictitating membrane. Separate control groups received either (a) no CS or US, (b) CS-alone, or (c) completely random presentations of CS and US. Few CRs occurred in the experimental group at the outset of conditioning, but the percentage of CRs during the second half of the first acquisition session exceeded 95%. Conditioning stabilized above 95% CRs during Acquisition Sessions 3 through 7. These responses could not be attributed to pseudoconditioning, sensitization, or other nonassociative factors. When the experimental group was subsequently given six CS-alone sessions, the course of extinction was gradual. Most results seemed similar to those previously obtained during classical conditioning of the nictitating membrane in rabbits.     

Conditioning in human opiate addicts

Eight volunteers maintained on daily methadone participated in a classical conditioning procedure to determine which if any of the elements of narcotic withdrawal could be conditioned. The unconditioned stimulus was the injection of a small dose of naloxone. The unconditioned response was a brief precipitated withdrawal syndrome. The conditioning stimulus was a tone, odor, and injection of saline. Conditioning was successful in the pilot study in 5 of 8 subjects. The conditioned response consisted of tearing, yawning, lacrimation, systolic blood pressure increase, respiratory irregularities and subjective feelings of narcotic withdrawal sickness (nausea, muscle aches, chills). A second group of 8 subjects showed, in addition to the above, evidence of conditioning of heart rate, respiratory rate and skin temperature decrease. These laboratory findings support the clinical reports of a conditioned withdrawal syndrome and suggest ways to improve treatment results by detecting and extinguishing or modifying conditioned responses.     

Posttraining prefrontal lesions impair jaw movement conditioning performance,but have no effect on accompanying heart rate changes

This experiment examined the role of the medial prefrontal cortex (mPFC) in regulating learned autonomic and somatomotor responses in rabbits using appetitive Pavlovian conditioning. Interstimulus interval (ISI) duration [i.e., the time between the onset of the conditioned stimulus (CS) and unconditioned stimulus (US)] was manipulated in order to determine whether ISI duration was related to the heart rate (HR) responses obtained during conditioning. Two groups received either a 1- or a 4-s ISI, with a tone as the CS and an intraoral pulse of water as the US. Another two groups received explicitly unpaired presentations of either the 1- or 4-s tone CS and water US. Few conditioned jaw movement (JM) or HR conditioned responses (CRs) were observed in the unpaired conditions. Significant JM conditioning was, however, elicited by the paired conditions, especially to the 4-s ISI. Consistent CS-evoked HR accelerations were observed in both ISI conditions. After five sessions of training, the mPFC was lesioned in half the animals. A separate group of paired animals received sham lesions. After surgical recovery, all animals received 3 days of postoperative training. During the first postoperative training session, JM CRs significantly declined in both groups with mPFC lesions in comparison to the groups with sham lesions. The mPFC lesions, however, did not affect the CS-evoked cardiac accelerations, which again occurred during postoperative training.     

Developmental changes in eyeblink conditioning and neuronal activity in the pontine nuclei

Neuronal activity was recorded in the pontine nuclei of developing rats during eyeblink conditioning on postnatal days 17–18 (P17–P18) or P24–P25. A pretraining session consisted of unpaired presentations of a 300-msec tone conditioned stimulus (CS) and a 10-msec periorbital shock unconditioned stimulus (US). Five paired training sessions followed the unpaired session, consisting of 100 trials of the CS paired with the US. The rats trained on P24–P25 exhibited significantly more conditioned responses (CRs) than the rats trained on P17–P18, although both groups produced CRs by the end of training. Ontogenetic increases in pre-CS and stimulus-elicited activity in the pontine nuclei were observed during the pretraining session and after paired training. The activity of pontine units was greater on trials with CRs relative to trials without CRs in rats trained on P24–P25, but almost no CR-related modulation was observed in the pontine units of rats trained on P17–P18. The findings indicate that pontine neuronal responses to the CS and modulation of pontine activity by the cerebellum and red nucleus undergo substantial postnatal maturation. The developmental changes in pontine neuronal activity might play a significant role in the ontogeny of eyeblink conditioning.     

Conditioning the unconditioned response: modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus (US) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit nictitating (Oryctolagus cuniculus) membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or US manipulation. CRM occurred after 12 days of CS-US pairings but not following unpaired CS/US presentations or restraint. CRM survived CS-alone and CS/US-unpaired extinction of the conditioned response (CR) but not presentations of the US alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning.     

Fear Develops to the Conditioned Stimulus and to the Context during Classical Eyeblink Conditioning in Rats

In classical eyeblink conditioning, non-specific emotional responses to the aversive shock unconditioned stimulus (US), which are presumed to coincide with the development of fear, occur early in conditioning and precede the emergence of eyeblink responses. This two-process learning model was examined by concurrently measuring fear and eyeblink conditioning in the freely moving rat. Freezing served as an index of fear in animals and was measured during the inter-trial intervals in the training context and during a tone conditioned stimulus (CS) presented in a novel context. Animals that received CS-US pairings exhibited elevated levels of fear to the context and CS early in training that decreased over sessions, while eyeblink conditioned responses (CRs) developed gradually during acquisition and decreased during extinction. Random CS-US presentations produced a similar pattern of fear responses to the context and CS as paired presentations despite low eyeblink CR percentages, indicating that fear responding was decreased independent of high levels of learned eyeblink responding. The results of paired training were consistent with two-process models of conditioning that postulate that early emotional responding facilitates subsequent motor learning, but measures from random control animals demonstrate that partial CS-US contingencies produce decrements in fear despite low levels of eyeblink CRs. These findings suggest a relationship between CS-US contingency and fear levels during eyeblink conditioning, and may serve to clarify further the role that fear conditioning plays in this simple paradigm.     

A pitfall for the expectancy theory of human eyelid conditioning

Two simple eyeblink conditioning experiments with random intermittent reinforcement schedules were performed. In Experiment 1, subjects had to rate their expectancy for an unconditioned stimulus (US) on a seven-level scale prior to each trial. As anticipated, expectancy for US increased with a successive conditioned stimulus (CS) alone, and decreased with successive CS-US pairings. However, Experiments 1 and 2 showed that the frequency of eyeblink conditioned responses (CRs) evolved in a direction opposite to that of expectancy changes: CRs increased, whereas expectancy for US decreased, and vice versa. The possible effect of sensitization on eyeblink response was ruled out by the lack of a run effect in an unpaired control group in Experiment 2. These results tend to disconfirm the expectancy theory of conditioning. Although they were explicitly predicted by the conventional “strength” theory of conditioning, an alternative interpretation is proposed within a cognitive framework.     

Fear develops to the conditioned stimulus and to the context during classical eyeblink conditioning in rats

In classical eyeblink conditioning, non-specific emotional responses to the aversive shock unconditioned stimulus (US), which are presumed to coincide with the development of fear, occur early in conditioning and precede the emergence of eyeblink responses. This twoprocess learning model was examined by concurrently measuring fear and eyeblink conditioning in the freely moving rat. Freezing served as an index of fear in animals and was measured during the inter-trial intervals in the training context and during a tone conditioned stimulus (CS) presented in a novel context. Animals that received CS-US pairings exhibited elevated levels of fear to the context and CS early in training that decreased over sessions, while eyeblink conditioned responses (CRs) developed gradually during acquisition and decreased during extinction. Random CS-US presentations produced a similar pattern of fear responses to the context and CS as paired presentations despite low eyeblink CR percentages, indicating that fear responding was decreased independent of high levels of learned eyeblink responding The results of paired training were consistent with two-process models of conditioning that postulate that early emotional responding facilitates subsequent motor learning, but measures from random control animals demonstrate that partial CS-US contingencies produce decrements in fear despite low levels of eyeblink CRs. These findings suggest, a relationship between CS-US contingency and fear levels during eyeblink conditioning, and may serve to clarify further the role that fear conditioning plays in this simple paradigm.     

The incubation theory of fear/anxiety: experimental investigation in a human laboratory model of Pavlovian conditioning

The aim of this work was to test Eysenck's incubation theory of fear/anxiety in human Pavlovian B conditioning of heart rate (HR) responses. The conditioned stimuli (CSs) were phobia-relevant slides (snakes and spiders) and the unconditioned stimuli (UCSs) were aversive noises. The subjects were presented with two levels of noise intensity during acquisition and three levels of nonreinforced CS presentation (CS-only) in a delay differential (CS+/CS-) conditioning paradigm (2 x 3 x 2). Consistent with the incubation theory, conditioned HR acceleratory responses were sustained (resistance to extinction) for high-noise intensity and short-presentations of CS-only subjects. During the extinction phase, HR acceleratory responses quickly extinguished in low-noise intensity groups after the first presentations of CS-only. These findings were interpreted as support for the incubation theory of phobic fear.     

Role of the hippocampus in blocking and conditioned inhibition of the rabbit's nictitating membrane response.

Bilateral aspiration of the dorsal hippocampus produced a disrupttion of blocking of the rabbit's nictitating membrane response in Kamin's two-stage paradigm (Experiment 1) but had no effect on the formation of a Pavlovian conditioned inhibitor (Experiment 2). The results of Experiment 1 indicated that normal animals and those with cortical lesions given conditioning to a light-plus-tone conditioned stimulus (CS) gave conditioned responses (CRs) to both the light and the tone during nonreinforced presentations of each (test phase). If, however, compound conditioning was preceded by tone acquisition, only the tone elicited a CR during testing; that is, blocking was observed. In rabbits with hippocampal lesions, however, CRs were given to both the light and the tone during testing whether or not compound conditioning was preceded by tone acquisition. The data from Experiment 2 showed that rabbits with hippocampal lesions could discriminate as well as normal rabbits and those with cortical lesions between a light (CS+) and light plus tone (CS-). In addition, when the inhibitory tone was subsequently paired with the unconditioned stimulus in retardation testing, animals in all three lesion conditions acquired the CR at the same rate. Thus, it appears that hippocampal lesions do not disrupt conditioned inhibition. The results of these experiments were taken as support for the view that the hippocampus is responsible for "tuning out" stimuli that have no adaptive value to the organism.     

Compensatory and mimetic conditioned responses to effects of heroin in addicted persons

Study 1: The aim of this study was to analyze in persons detoxified of heroin, compensatory conditioned responses (CCRs) that are opposite to the unconditioned physiological, and subjective effects that are induced by this substance. The procedure consisted in presenting slides with images of neutral stimuli (NSs) and conditioned stimuli (CSs) of heroin to both non-addicted and detoxified addicted persons. The evaluated responses were heart rate (HR) and desire for heroin (DH). Study 2: The aim was to facilitate the emission of mimetic conditioned responses (MCRs) to the unconditioned physiological, and subjective effects of heroin in detoxified heroin addicts. Three different stimulus series were manipulated: SA, during which the participant remained alone; SB, administration of a needle prick given by the researcher; SC, performance of the "pump" ritual without drug by the participants. The responses measured were HR and DH. The results of both studies are considered, respectively, to be indicators of compensatory and mimetic conditioned responses.     

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.     

Conditioned nausea after cancer chemotherapy and autonomic nervous system conditionability

There are marked individual differences in conditioned nausea after cancer chemotherapy. To examine if part of this variation is associated with individual differences in autonomic nervous system conditionability, the present study addressed whether patients with conditioned nausea acquired conditioned heart rate and electrodermal responses at a different rate than patients without conditioned nausea. Of 28 relapse-free patients who had completed cisplatinum treatment for testicular cancer between 1981 and 1986, 10 reported persistent conditioned nausea, 8 extinguished conditioned nausea and 10 no conditioned nausea. These three groups were subjected to a differential conditioning paradigm with 8 sec pictorial stimuli (circles and triangles) serving as conditioned stimuli for an unconditioned electric shock while heart rate and electrodermal activity was monitored. There were 4 habituation, 8 acquisition and 8 extinction trials with each of the two cues. Analyses of variance using nausea status as the independent variable and physiological responses as the dependent lended some support to the notion that conditioned heart rate deceleration developed in response to the reinforced compared to the nonreinforced cue during acquisition in the two groups with persistent or extinguished conditioned nausea but not in the group with no conditioned nausea. In addition, patients that displayed good, as compared to poor heart rate conditionability during acquisition, were more likely to have persistent conditioned nausea, whereas those who showed poor heart rate conditioning mostly were those without conditioned nausea. Electrodermal variables revealed no systematic differences between groups. This tentatively supports that individual differences in parasympathetic but not sympathetic nervous system conditionability may be associated with individual differences in conditioned nausea resulting from cancer chemotherapy.     

"Pseudoconditioned" jaw movements of the rabbit reflect associations conditioned to contextual background cues.

Two experiments employing 180 rabbits and involving tone conditioned stimuli (CSs) and intraoral water unconditioned stimuli (UCSs) investigated pseudoconditioning of jaw movement. CS-alone, UCS-alone, paired CS-UCS, and four explicitly unpaired CS-UCS treatments were compared to no stimulus presentation. UCS-alone presentations were sufficient to produce pseudo-CR (conditioned response) acquisition. Pseudo-CRs were retained and gradually extinguished over 30 days of CS-alone presentations. Random sequences of unpaired CSc and UCSs produced higher pseudo-CR frequencies than fixed sequences. A pseudo-CR partial reinforcement extinction effect was observed. Background extinction, that is, simply confining the subject in the experimental environment without stimulation, was effective in extinguishing both pseudo-CRs and CRs. Pseudo-CR results could not be attributed to CS-UCS trace conditioning, sensory preconditioning, second-order conditioning, or intra-analyzer conditioning. Results indicate that the associative mechanisms underlying pseudoconditioning phenomena involve conditioning of associations to contextual background (apparatus, trace, temporal, and sequential aftereffect) cues by UCS-alone and unpaired UCS presentations.     

Concomitant Pavlovian conditioning of heart rate and leg flexion responses in the rat

Pavlovian conditioning was studied in male Fischer 344 rats using tones as the conditioned stimulus (CS) and footshock as the unconditioned stimulus (UCS). Different groups of animals received (a) contiguous CS-UCS pairings with a 0.5 sec CS, (b) contiguous CS-UCS pairings with a 4.0 sec CS, or (c) a random sequence of noncontiguous tones and shocks using either a 0.5 sec or a 4.0 sec CS. Heart rate (HR) and leg flexion (LF) responses were recorded. Leg flexion conditioning occurred only in the 0.5 sec contiguous group. Decelerative HR CRs occurred only in the 4.0 sec contiguous group. Accelerative HR changes occurred in the other two groups but were significantly greater in the 0.5 sec contiguous group. These results are similar to but not identical to those obtained during eyeblink or nictitating membrane conditioning in rabbits, and suggest that the topography of the Pavlovian HR CR is dependent on the simultaneous occurrence of other classically conditioned responses.     

Discriminative conditioning alters food preferences in the leech, Haemopis marmorata

The feeding behavior of the carnivorous leech, Haemopis marmorata, was aversively trained in a discriminative classical conditioning task. Two conditioned stimuli were used: One consisted of a food (chicken or liver) paired with an unconditioned stimulus of quinidine (bitter chemical); the other consisted of the alternate food presented in an unpaired relationship with the quinidine. Training consisted of alternating exposures to the two conditioned stimuli. Testing consisted of the simultaneous presentation of a conditioned stimulus food and a neutral food, beef. The percentages of responding to the conditioned stimuli were tabulated. Haemopis could discriminate between the conditioned stimuli. As a result of pairing a food with quinidine, the leeches selectively reduced their preference for that paired food, while they did not alter their preference for the unpaired food.     

The Effect of Counterconditioning on Evaluative Responses and Harm Expectancy in a Fear Conditioning Paradigm

In fear conditioning, extinction targets harm expectancy as well as the fear response, but it often fails to eradicate the negative affective value that is associated with the conditioned stimulus. In the present study, we examined whether counterconditioning can serve to reduce evaluative responses within fear conditioning. The sample consisted of 70 nonselected students, 12 of whom were men. All participants received acquisition with human face stimuli as the conditioned stimuli and an unpleasant white noise as the unconditioned stimulus. After acquisition, one third of the sample was allocated to an extinction procedure. The other participants received counterconditioning with either a neutral stimulus (neutral tone) or a positive stimulus (baby laugh). Results showed that counterconditioning (with both neutral and positive stimuli), in contrast to extinction, successfully reduced evaluative responses. This effect was found on an indirect measure (affective priming task), but not on self-report. Counterconditioning with a positive stimulus also tended to enhance the reduction of conditioned skin conductance reactivity. The present data suggest that counterconditioning procedures might be a promising approach in diminishing evaluative learning and even expectancy learning in the context of fear conditioning.     

Excitatory conditioning of individual Drosophila melanogaster

Testing individual animals from a heterogenic population of Drosophila melanogaster, we demonstrate conditioning of the proboscis extension reflex. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses over trials, (b) measured differences in performance levels among individual subjects, and (c) a sex difference, with more males conditioned than females, and those that did did so more quickly. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned or unconditioned stimuli directly affected the conditioned response, whereas unconditioned stimulus preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the unconditioned stimulus. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large number of individuals that can be tested simultaneously on the automated stimulation apparatus, it is now possible to make precise behavioral measurements on samples large enough for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype.     

Classical conditioning of the eyeblink response in the delay paradigm in adults aged 18-83 years

To determine if age differences in classical conditioning of the eyelid response begin to appear in middle age in humans as they do in animals, adult subjects aged 18-83 years were trained in the delay conditioning paradigm. Large age effects occurred. Statistically significant differences first appeared in the decade of the 40s. Within-age-group variability was large. To reduce variability, subjects were classified by the magnitude of their unconditioned response (UR). Regardless of age, subjects with low amplitude URs conditioned poorly. In the normal UR amplitude group, the correlation between age and total percentage conditioned responses (CRs) was -.58. Eyeblink rate and voluntary responding did not account for age differences in conditioning, and it was unlikely that hearing acuity or corneal sensitivity caused the differences. Parallels between human and animal eyelid conditioning are considered, and it is suggested that age changes in the cerebellum may affect conditioning in aging mammals, including humans.