Effects of quinpirole on behavioral extinction

Behavioral effects of quinpirole (QNP), a dopamine D(2) receptor agonist, suggest it impacts neural mechanisms mediating goal-directed behaviors, as well as behavioral extinction following removal of a primary reinforcer. The present study investigated the effect of QNP on behavioral extinction following the omission of contingent reinforcement, and whether this effect is related to acquisition or processes specific to extinction. Rats were trained on a continuous reinforcement schedule to nose-poke for water reward. Using a free-operant procedure, rats completed approximately 70 responses for each of four consecutive days. On the fifth day reward was withheld. Rats were assigned to one of five groups in which they received 0.3 mg/kg QNP ip either during the first day (acquisition phase), the second 2 days (maintenance phase), the last day (extinction phase), or during all days. A fifth group received vehicle injections. Rats receiving QNP during the acquisition and maintenance phase did not differ significantly from the control group during the extinction phase, although they demonstrated reduced response rates on days they received QNP. However, rats treated during the extinction phase or during all phases demonstrated a significant reduction in the rate of extinction. This effect cannot be attributed to an increase in general behavioral arousal because response rates for reinforced responses did not differ significantly among groups following acquisition of the behavior. The reduced extinction effect does not appear to be related to abnormalities in the initial behavior-reward association, but instead may result from enhanced engagement of learned behavioral patterns, or from interference of signals associated with removal of predicted reinforcement.     

Cognitive factors and CS-UCS interval effects in the differential conditioning and extinction of skin conductance responses

Mandel and Bridger (1967) found resistance to extinction of differentially conditioned skin conductance responses by subjects, who, according to a post-conditioning questionnaire, believed pre-extinction instructions that the shock-UCS would no longer be administered. The present study was intended to: (1) determine whether or not an extraordinarily noxious shock-UCS is required to produce such results; (2) eliminate possible retrospective falsification effects associated with the use of a post-conditioning questionnaire by monitoring subjects' UCS expectancies continuously throughout extinction as well as acquisition trials; (3) attempt to confirm that resistance to extinction is stronger with a 0.5 sec CS-UCS interval than with an 8 sec interval; and (4) test several predictions regarding UCS expectancies during the intertrial intervals of acquisition. After receiving 16 instructed acquisition trials, two groups (N = 20 in each) exposed to either a 0.5 sec or 8 sec CS-UCS interval were fully instructed regarding discontinuation of the UCS during the pending 20 extinction trials. Reliable differential conditioning was obtained during the first extinction trial block for subjects who, according to the expectancy monitoring measure as well as a post-conditioning questionnaire, did not expect UCS administration. The extent of resistance to extinction did not differ between the two groups. Consistent with predictions from a cognitive viewpoint, the expectancy monitoring data of the two groups differed significantly during the intertrial intervals of acquisition.     

Conditioned diastolic blood pressure: the effects of magnitude of acquired response and feedback schedules on resistance to extinction

The purpose of this experiment was to examine the effects of: (a) training to two different response magnitude criteria, and (b) three different feedback schedules on the acquisition and subsequent extinction of diastolic blood pressure changes. Subjects were 20 male and female normotensive volunteer college students, ages 18-36 years. A 3 x 2 design was used in which 3 schedules of reinforcement (0, 50 and 100%) were factorially compared with two response magnitude training criteria (10% and 20% of resting basal diastolic blood pressure). The results indicated that while the partial reinforcement effect appears to hold for the acquisition of bidirectional diastolic blood pressure changes, different response magnitude training criteria seemed to have a greater influence in producing significant differences in acquisition rate during the training of diastolic blood pressure decreases. Resistance to extinction was notably weak across all conditions, with most subjects failing to exhibit previously acquired bidirectional diastolic blood pressure performance after the end of the first extinction session.     

Gonadal hormones and effects of partial reinforcement on appetitive behaviour in the rat

Two experiments are reported in which rats were run in the straight alley with partial (PR) or continuous (CR) food reinforcement during acquisition and then extinguished. Hormone treatment (with estradiol benzoate, EB, or testosterone propionate, TP) was given during acquisition on both CR and PR schedules, but not during extinction. The results showed no effect of EB on the partial reinforcement extinction effect (PREE) in female rats. In males TP was found to reduce the PREE by differentially reducing resistance to extinction in the PR condition. Thus TP but not EB attenuates the behavioural effects of nonreward.     

Learning to fear suffocation: a new paradigm for interoceptive fear conditioning

The present study aimed to establish a new interoceptive fear conditioning paradigm. The conditioned stimulus (CS) was a flow resistor that slightly obstructs breathing; the unconditional stimulus (US) was a breathing occlusion. The paired group (N = 21) received 6 acquisition trials with paired CS–US presentations. The unpaired group (N = 19) received 6 trials of unpaired CS–US presentations. In the extinction phase, both groups were administered 6 CS‐only trials. Measurements included startle eyeblink response, electrodermal responses, and self‐reported US expectancy. In the paired group, startle blink responses were larger during CS compared to intertrial interval during acquisition and extinction. Electrodermal and US expectancies were larger for the paired than for the unpaired group during acquisition, but not during extinction. The present paradigm successfully established interoceptive fear conditioning with panic‐relevant stimuli.     

Retention under changed-reward conditions of persistence learned by infant rats

Two experiments were performed to determine whether or not persistence acquired under reinforcement conditions of infancy can be retained and transferred to adult reinforcing conditions. In Experiment I 2 groups of rats 14–15 days of age were trained in a runway under a partial (PRF) or continuous (CRF) schedule of milk-suckling reinforcement. A 3rd group was trained under continuous nonreinforcement (NRF) conditions. The PRF and CRF groups acquired the approach response about equally, and the NRF showed a very small increase in speed. In immediate extinction, the PRF group was more resistant to extinction than its CRF counterpart. For the NRF group “extinction” produced a continuation of the low-level “acquisition” performance. Experiment II showed that persistence acquired at 14–15 days with milk-suckling reinforcement can be sustained through a 2-week retention period including a phase of CRF food-pellet reward.     

Effects of acute trimethyltin exposure on appetitive acquisition and extinction performance in the adult rat

Adult male rats were given one intragastric infusion of either 7 mg/kg trimethyltin chloride (dose calculated as the base of trimethyltin [TMT]) or physiological saline. Twenty-one days after dosing, subjects from each condition were divided into two equal-sized groups and trained with either partial (PRF) or continuous (CRF) reinforcement in a straight alley maze. The acquisition phase of training, lasting 40 trials (4 trials/day), was followed by 20 trials of extinction training (4 trials/day). Analyses performed on total speed revealed that TMT-treated subjects performed at lower levels during acquisition than controls regardless of schedule condition. Also, the rate of resistance to extinction was significantly reduced for treated subjects compared with that of controls regardless of the training schedules used during acquisition. A partial reinforcement extinction effect was observed for both control and TMT-treated subjects, that is, independent of dose regimen; PRF training occasioned greater persistence during extinction than did CRF training. These findings are discussed in terms of their implications for contemporary empirical and theoretical issues relating to TMT-induced hippocampal lesions.     

Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning

Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is differentially involved in these processes.     

The Onset of Contingency Awareness and Electrodermal Classical Conditioning: An Analysis of Temporal Relationships during Acquisition and Extinction

The temporal relationship between the onset of contingency awareness and the onset of discrimination classical conditioning of the skin conductance response was evaluated. Awareness of the CS-UCS contingencies and skin conductance responses were measured trial-by-trial from 60 college student subjects during both acquisition and extinction. In addition, the conditioning paradigm was embedded within a masking task in order to delay the onset of awareness so that preaware and postaware trials could be analyzed. Two skin conductance responses were measured, a short latency first interval response (FIR) and a longer latency second interval response (SIR). Results showed that: 1) the onset of FIR discrimination conditioning began only after subjects indicated awareness of both the positive (CS+) and the negative (CS?) contingencies, 2) concurrent with the onset of this awareness, a) FIR discrimination increased suddenly due to increased responding to CS+ while b) SIR discrimination also increased suddenly for some subjects but gradually developed for others, 3) FIR extinction occurred only among subjects who exhibited expectancy extinction, and was due to decreased responding to CS+. The results are consistent with the interpretation that FIR discrimination is related to the cognitive processing of the CSs’significance, and that SIR discrimination is related to an individual difference variable which was reflected in the rate at which subjects became aware.     

OPERANT CONDITIONING OF THE HUMAN SALIVARY RESPONSE

To demonstrate operant conditioning of the human salivary response, stimulus control was attempted. Unstimulated parotid saliva was collected from 4 Ss under two reinforcement schedules. Continuous reinforcement (CRF) alternated at regular intervals with differential reinforcement for zero responding (DRO)– reinforcement for non-responding during a specified time period. Cumulative records revealed an increase in responding under CRF and a decrease in responding under DRO for 3 of the 4 Ss. Swallowing was recorded. The conditioned salivary response appeared not to be mediated by muscle response.     

Intolerance of uncertainty and threat generalization: A replication and extension

Intolerance of uncertainty (IU) is a transdiagnostic risk factor for internalizing disorders. Prior work has found that IU may be associated with either increased reactivity to threat or, alternatively, with decreased differential responding between threat and nonthreat/safety cues (i.e., threat generalization). For example, work by Morriss, Macdonald, & van Reekum  (2016) found that higher IU was associated with increased threat generalization during acquisition (using skin conductance response (SCR)), as well as less differentiation between acquisition and extinction (using subjective uneasiness ratings). Here, three labs attempted direct and conceptual replications of Morriss, Macdonald, et al. (2016). Results showed that the direct replication failed, despite being conducted at the same lab site as the original study; moreover, in contrast to Morriss, Macdonald, et al. (2016), the direct replication found that higher IU was associated with greater SCR discrimination between threat and safety cues (across acquisition and extinction), as well as greater differences in uneasiness ratings between acquisition and extinction. Nonetheless, in the conceptual replications, higher IU was associated with greater threat generalization, as well as less discrimination between acquisition and extinction, as measured using SCR. Higher IU was also associated with larger late positive potentials to threat versus safety cues during extinction—results that mirror those observed by Morriss, Macdonald, et al. (2016) using SCR. Results are discussed with regards to the challenge involved in defining a successful replication attempt, the benefits of collaborative replication and the use and reliability of multiple measures.     

The Effects of Directional Facial Cues on Electrodermal Conditioning to Facial Stimuli

The present two Experiments demonstrate that the orientation of angry facial expressions is a critical cue when faces serve as conditioned stimuli during aversive electrodermal conditioning. Experiment 1 demonstrated that responses conditioned to angry faces directed toward the subjects showed significant resistance to extinction whereas responses conditioned to angry faces directed away extinguished immediately during extinction. Experiment 2 was designed to investigate whether the orientation factor was effective only during extinction, i.e. whether the orientation was a performance variable, or if the observed effect originated from factors active during acquisition, i.e. if the orientation primarily influenced learning. When the orientation was shifted between the acquisition and the extinction phase, it was found that it did not matter what direction the faces had during acquisition; it was only during extinction that the faces needed to be directed toward the subjects to evoke persistent responding. These results suggest that the subjects acquired a conditioned response to the angry face regardless of its direction, but that this learning effect remained only when the angry face was directed toward the subject during extinction.     

Acquisition and extinction of an operant response in differentially reared rats

Rats reared in either socially isolated or control environments were trained to bar press for food on a variable interval schedule of reinforcement, beginning at 125 days of age for 37 consecutive days. Following this phase the subjects were tested for response persistence during an extinction test. Next, the subjects were compared on measures of spontaneous recovery and the rate of response reacquisition when the reinforcement contingencies were once again reinstated. Though no differences were discerned between the groups on measures of acquisition, maintenance, and reacquisition, isolated rats emitted many more responses than the controls during extinction testing.     

Extinction after regular and irregular reward schedules in the infant rat: Influence of age and training duration

Greater persistence in extinction is observed following inconsistent reward compared to that observed following consistent reward, an effect termed the partial reinforcement extinction effect (PREE). We report three experiments in which the extinction rates of random partially reinforced (PRF) or continuously reinforced (CRF) infant rat pups were compared to the extinction rate of pups trained with an alternative and regular schedule of partial reinforcement, known as patterned single alternation (PSA). In PSA, subjects learn to alternate speed of responding in anticipation of the regular alternation of reward and nonreward trials in the straight alley runway. In Experiment 1, 17‐day‐old PSA subjects showed CRF‐like extinction rates; whereas in Experiment 2, in which extinction was initiated early in training prior to the onset of the PSA discrimination, PSA subjects showed prolonged, PRF‐like extinction curves. In contrast, 12‐day‐old pups in Experiment 3 showed no reward‐schedule‐related differences in extinction, despite differences in behavior during acquisition. These results prompt a modification of Amsel's (1962) model of discrimination learning, and suggest the existence of a dissociation between different types of reward‐related expectancies in the younger subjects. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 57–70, 1999     

Adrenalectomy eliminates the extinction spike in autoshaping with rats

Experiment 1, using rats, investigated the effect of adrenalectomy (ADX) on the invigoration of lever-contact performance that occurs in the autoshaping situation after a shift from acquisition to extinction (called the extinction spike). Groups of rats with ADX or sham operations were trained under spaced and massed conditions [average intertrial intervals (ITI) of either 15 or 90 s] for 10 sessions and then shifted to extinction. ADX did not affect acquisition training but it eliminated the extinction spike. Plasma corticosterone levels during acquisition were shown in Experiment 2 to be similar in rats trained under spaced or massed conditions. Adrenal participation in the emotional arousal induced by conditions of surprising nonreward (e.g., extinction) is discussed.     

Cytotoxic lesions of the retrohippocampal region attenuate latent inhibition but spare the partial reinforcement extinction effect

 Experiment 1 assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate. Received: 13 June 1996 / Accepted: 24 December 1996     

Behavioral and neuroanatomical effects of prenatal, postnatal, or combined exposure to ethanol in weanling rats

Separate and combined effects of prenatal and postnatal exposure to ethanol on activity, emotionality, learning, and hippocampal neuroanatomy were examined in infant rats. Neonatal rats from mothers that were fed either a liquid ethanol (E) or control (C) diet on Gestational Days (G) 1-21 were artificially reared during Postnatal Days (P) 4-12 on either 3% ethanol (E) or isocaloric maltose/dextrin (C) in a milk formula. Pups in these treatment groups (EE, EC, CE, and CC) were tested for activity and emotionally in an open field on P19, for acquisition and extinction of an appetitive, straight runaway task on P20-P21, and for the effects of ethanol treatments on alterations in hippocampal neuroanatomy on P21. Differences in activity and emotionally were slight. Ethanol affected both the partial reinforcement acquisition effect and the partial reinforcement extinction effect. Hippocampal cell density (compared with Group CC) showed a 12% reduction in CA1 pyramidal cells and an 11% reduction in mature granule cells in Groups EC and EE; the CA4 area (compared with Group CC) was significantly larger after postnatal exposure (Groups CE and EE). Significant positive correlations were found between rate of extinction after partial reinforcement (PRF) training and CA1 pyramidal cell density in Groups CC and CE. A significant negative correlation was found between extinction rate after PRF training and CA4 area in Group EE.     

Plasma corticosterone levels during extinction of a lever-press response in hippocampectomized rats

Male Long-Evans rats with bilateral lesions of the hippocampus or of the cortex overlying the hippocampus and unoperated rats were trained to lever press for water reinforcement on a continuous reinforcement schedule, and then extinguished. The hippocampectomized animals responded at higher rates than controls during early acquisition sessions, the difference decreasing over training and increasing again during extinction. Plasma levels of corticosterone were determined in the resting (non-stressed) state on ad lib and deprivation watering schedules, and following ether anesthesia, exposure to a novel environment, a reinforced operant session and the first extinction operant session. The results indicated that hippocampal lesions produced by aspiration cause no essential deficit in pituitary-adrenal function. However, the hippocampectomized rats failed to exhibit the normal elevation of plasma corticosterone during the first extinction session. This finding contradicts proposals that hippocampectomy increases the frustrative-emotional response to unmet reward expectancies. It is supportive of attentional process theories of hippocampal function.     

CLASSICAL CONDITIONING OF THE GALVANIC SKIN RESPONSE IN IMMOBILIZED CATS

Ten cats were immobilized with Flaxedil and given either paired conditioning trials or unpaired presentations of the CS and UCS in a study of classical GSR conditioning. The paired group received 5 adaptation trials followed by 40 paired tone-shock acquisition trials and 10 extinction trials. A pseudo-conditioning control group received unpaired trials with tone and shock, to control for pseudoconditioning and sensitization. It was found that the group receiving paired conditioning trials responded at a significantly higher magnitude than did control Ss, thus demonstrating classical conditioning in this preparation. Electromyograms were recorded for all Ss during the experimental sessions to monitor skeletal movements. The level of immobilization was such that no movements were seen in response to the CS. Analysis of the baseline skin resistance data revealed no significant differences which could have contributed to group differences in GSR magnitudes. It is concluded that skeletal movement was not a necessary concomitant of classical conditioning of the GSR.     

Cardiovascular and Electrodermal Responses Conditioned to Fear-Relevant Stimuli

This study examined heart rate, finger pulse volume, and skin conductance responses in subjects conditioned to fear-relevant (snakes and spiders) and fear-irrelevant (flowers and mushrooms) slide stimuli by an electric shock unconditioned stimulus. A differential conditioning paradigm with an interstimulus interval of 8 sec was used. There were 4 habituation, 8 acquisition, and 20 extinction trials with each of the two cues. The results demonstrated reliable acquisition for finger pulse volume and skin conductance responses, with superior resistance to extinction for the fear-relevant conditioned stimuli. The heart rate data showed no differentiation between reinforced and nonreinforced cues during acquisition and extinction, and no effect of fear-relevance. This discrepancy between skin conductance and finger pulse volume responses, on the one hand, and heart rate, on the other, was interpreted as due to differences in innervation, with the former measures mainly reflecting sympathetic and the latter parasympathetic effects.