Disruption of noradrenergic, but not serotonergic or opiate, functioning blocks both cardiac and behavioral components of the orienting response in preweanling rats

Previous work in this laboratory established that selective attention, as measured by the behavioral and autonomic expressions of the orienting response (OR), is not disrupted by either dopaminergic or cholinergic receptor blockade. The present experiments extended this pharmacological analysis of the OR. In Experiment 1, preweanling rats were injected with methysergide maleate, a serotonin receptor blocker. Neither the behavioral nor the heart rate (HR) component of the OR was attenuated. In Experiment 2, the opiate receptor blocker naltrexone also failed to inhibit the HR and behavioral expressions of the OR. alpha-1 adrenergic receptor blockade with WB-4101 in Experiment 3 abolished both the HR and behavioral ORs to the pulsating tone. In Experiment 4, clonidine, which inhibits release of norepinephrine by stimulating alpha-2 autoreceptors, attenuated both behavioral and HR ORs to the pulsating tone in a dose-dependent manner. These data, in combination with the prior findings, suggest that norepinephrine is critically involved in the central process underlying the OR in the rat. Dopaminergic, cholinergic, serotonergic, and opiate receptor blockades do not impair selective attention as indexed by HR and behavioral ORs to an auditory stimulus. In contrast, disruption of noradrenergic functioning via either alpha-1 receptor blockade or alpha-2 receptor stimulation disrupts both the HR and behavioral components of the OR. These results indicate that integrity of central noradrenergic functioning is essential for expression of the OR and for stimulus-directed attention.     

In vitro reinforcement of hippocampal bursting: a search for Skinner's atoms of behavior.

A novel "in vitro reinforcement" paradigm was used to investigate Skinner's (1953) hypotheses (a) that operant behavior is made up of infinitesimal "response elements" or "behavioral atoms" and (b) that these very small units, and not whole responses, are the functional units of reinforcement. Our tests are based on the assumption that behavioral atoms may plausibly be represented at the neural level by individual cellular responses. As a first approach, we attempted to reinforce the bursting responses of hippocampal units in a highly reduced brain-slice preparation with local micropressure applications of behaviorally reinforcing dopaminergic drugs. The same injections were administered independently of bursting to provide a "noncontingent" control for nonspecific stimulation or facilitation of firing. It was found that the bursting responses of individual CA1 pyramidal neurons may be progressively facilitated in a dose-related manner by response-contingent (but not noncontingent) injections of dopamine itself, the dopamine D1-preferring agonist SKF 82958, the D3-preferring agonist quinpirole, and the D2-like selective agonist (+)-4-propyl-9 hydroxynapthoxazine. These findings support the conclusion that unit bursting responses can be reinforced in vitro in hippocampal slices, and they further suggest that the same dopamine receptor subtypes are involved in both cellular and behavioral operant conditioning. The results thus provide indirect support for Skinner's atoms-of-behavior hypothesis.     

A cellular analogue of operant conditioning.

Using the hippocampal-slice preparation, we attempted to model operant conditioning in vitro by reinforcing pyramidal cell bursting responses with local micropressure applications of transmitters and drugs. The same injections were administered independently of bursting to provide a "noncontingent" control for direct pharmacological stimulation or facilitation of firing. The results suggested that the bursting responses of individual CA1 pyramidal neurons may be reinforced in a dose-related manner by response-contingent (but not noncontingent) injections of dopamine and the selective dopamine D2 agonist, N-0923. N-0924, a stereoisomer of N-0923 that is largely devoid of D2-agonist activity, failed to reinforce CA1 bursting. Burst-contingent injections of the excitatory neurotransmitter glutamate also failed to reinforce CA1 bursting; indeed, the glutamate applications (whether contingent or random) reduced the likelihood of bursts while increasing the frequency of solitary spikes. Reinforcement delays exceeding 200 ms largely eliminated the reinforcing efficacy of the D2 agonist N-0437 in CA1 operant conditioning. The results are consistent with the suggestion that the behaviorally reinforcing effects of dopaminergic agents can be modeled in vitro in the hippocampal-slice preparation.     

Motives, values and moral judgments

This study examined McClelland's (1981) hypothesis that operant and respondent measures of personality are orthogonal and assess different dimensions of personality structure. An operant measure of motives, a sentence completion test, and two respondent measures of cognitive schema variables, the Rokeach Value Survey and the Defining issues Test, were administered to 311 subjects. As predicted and in support of McClelland's hypothesis, 69% of the correlations between the respondent measures were significant at the alpha .05 level of probability versus 14% of the correlations between the operant and respondent measures. Further, within the domain of cognitive schema variables, it was theoretically possible to predict which values would correlate with different levels of moral judgment. The findings were discussed in terms. of their implications for person x situation models of social interaction and the prediction of criterion variables from typologies of personality.     

Altering "motivational" variables alters induction produced by upcoming food-pellet reinforcement

Previous research has demonstrated that rats will increase their rates of lever pressing for sucrose rewards in the first half of an experimental session when food pellets, rather than the same sucrose, continually serve as the reward in the second half of the session. This effect has been coined induction, and the present study investigated whether it could be altered by altering "motivational" variables. Experiment 1 manipulated subjects' motivation by altering, across conditions, their level of food deprivation. Predictably, the size of induction varied directly with level of deprivation. Experiments 2 and 3 manipulated subjects' motivation by feeding them food pellets and sucrose, respectively, prior to their responding in the experimental session. These pre-session feedings decreased the size of the observed induction in both experiments. The results from the present study indicate that the size of induction is correlated with subjects' motivation to respond for the available reinforcers. They are also consistent with the idea that operant processes underlie the effect. The notion that induction might encompass the concept of "anticipation" is also discussed. Electronic Publication     

Bombesin improves rats' operant responding maintained by a differential-reinforcement-of-low-rates schedule of food reinforcement

The present study examined rats' responding on a differential-reinforcement-of-low-rates schedule of food reinforcement following intraperitoneal injections of various doses of bombesin (4, 6, 8, 16, 32 micrograms/kg). Analyses indicated that only the 6 micrograms/kg dosage improved DRL responding. The findings are consistent with prior research examining bombesin's effect on operant behavior and support the notion that bombesin induces satiety rather than malaise.     

Effects of D- and L-amphetamine on the predatory behavior of Southern grasshopper mice,onychomys torridus

Adult male and female southern grasshopper mice (Onychomys torridus) were tested for predatory aggression toward cricket prey 1 hr after single injections of d-amphetamine (1 or 10 mg/kg) or 1-amphetamine (1 or 10 mg/kg). At the lower dose, d-amphetamine decreased feeding behaviors, while I-amphetamine altered attack-related behaviors. At the higher dose, both stereoisomers appeared to be equipotent in significantly decreasing 5 measures of predatory aggression. These results suggest that brain dopamine and norepinephrine play important roles in the regulation of predatory aggression of Onychomys torridus.     

Positive and negative conditioned suppression in the pigeon: Effects of the locus and modality of the CS

In Experiment I, four pigeons were exposed to trials in which a 12-sec key light illumination was followed by free food. These trials were superimposed upon a baseline of key pecking for food reinforcement on a variable-interval schedule. When the signal for food was on the operant key, response rate was substantially higher during the signal than during the baseline procedure. When the signal was on a second, signal key, operant responding was suppressed during the signal and substantial pecking of the signal key occurred. The sum of signal key and operant key pecks far exceeded the operant baseline rate of responding. An explanation of opposite results obtained with rats and pigeons as subjects in experiments of this type was suggested in terms of the spatial relation between the signal for free food and the operant target which usually characterizes these experiments. Experiment II assessed the importance of signal location when shock rather than food was the US. Suppression of operant key pecking was unaffected by signal location. Experiment III assessed the relative effectiveness of visual and auditory stimuli (clicks) as signals for food and shock, and found that all combinations of signal and US were equally effective in suppressing operant key responding. The three experiments together suggested that the identification of important effects of species—typical behavior in one experimental situation does not imply that there will be like effects in similar situations.     

A PARADIGM FOR OPERANT CONDITIONING IN BLOW FLIES (PHORMIA TERRAE NOVAE ROBINEAU‐DESVOIDY, 1830)

An operant conditioning situation for the blow fly (Protophormia terrae novae) is described. Individual flies are trained to enter and reenter a hole as the operant response. Only a few sessions of contingent reinforcement are required to increase response rates. When the response is no longer followed by food, the rate of entering the hole decreases. Control procedures revealed that rate of responding is not a simple overall result of feeding or of aging. The flies entered into the hole only if the response was required to obtain the food.     

Defining reinforcess — A problem in communication for consultation in behavior modification

This paper reviews the respondent (Hull-Spence) and operant (Skinnerian) conditioning definitions of reinforcers and reinforcement and demonstrates the need to keep the systems separate when consulting about behavior modification. The two systems are shown to lead to different modification procedures.One important distinction between the systems is whether a reinforcer is simply associated with a response (respondent) or whether it must follow the response (operant). A second important distinction is the definition of negative reinforcement. In respondent conditioning, negative reinforcement entails presenting an aversive stimulus in association with the response and results in a decrease in response rate. In operant conditioning, negative reinforcement entails the removal of an aversive stimulus following a correct response, which results in an increase in response rate.     

Stimulus control: part I

In his effort to distinguish operant from respondent conditioning, Skinner stressed the lack of an eliciting stimulus and rejected the prevailing stereotype of Pavlovian "stimulus-response" psychology. But control by antecedent stimuli, whether classified as conditional or discriminative, is ubiquitous in the natural setting. With both respondent and operant behavior, symmetrical gradients of generalization along unrelated dimensions may be obtained following differential reinforcement in the presence and the absence of the stimulus. The slopes of these gradients serve as measures of stimulus control, and they can be steepened without applying differential reinforcement to any two points along the test dimension. Increases and decreases in stimulus control occur under the same conditions as those leading to increases and decreases in observing responses, indicating that it is the increasing frequency and duration of observation (and perhaps also of attention) that produces the separation in performances during discrimination learning.     

Potential noradrenergic targets for cognitive enhancement in schizophrenia

Substantial evidence suggests that alterations in noradrenergic function contribute to the cognitive impairments of schizophrenia. Activation of post-junctional alpha 2a-adrenergic receptors in the prefrontal cortex by the alpha 2a-selective agonist guanfacine has demonstrated some preliminary benefit in subjects with schizophrenia treated with atypical antipsychotics. alpha 1-adrenergic receptor activity may be less important in mediating the cognitive impairments of schizophrenia. beta-adrenergic receptors may serve as another potential target for cognitive remediation in schizophrenia. However, the potential increase in memory consolidation in schizophrenia patients produced by beta-adrenergic agonists may be outweighed by the impairment in cognitive flexibility and executive functioning produced by beta-adrenergic agonists. Finally, norepinephrine reuptake inhibitors, such as atomoxetine, hold promise as potential cognitive enhancers in schizophrenia because of their ability to indirectly but selectively increase extracellular dopamine concentrations in the prefrontal cortex.     

Rate and temporal pattern of key pecking under autoshaping and omission schedules of reinforcement

The role of response-reinforcer contiguity on autoshaped key pecking in pigeons was studied by scheduling response-dependent nonreinforcement at the beginning or the end of brief (8-sec) discrete trials. Schedules that permitted chance conjunctions of key pecking and food sustained high rates of responding, whereas those that prevented the occurrence of key peck-food intervals shorter than 4 sec sustained low response rates. In addition, selective reinforcement schedules supported accelerating or decelerating rates of responding within individual trials. These effects were traceable to response-reinforcer (operant), but not stimulus-reinforcer (respondent) factors.     

Efficacy of noradrenergic-selective agents in the treatment of neuropsychiatric diseases

In recent years, a number of antidepressants with varying degrees of selectivity for the noradrenergic neurotransmitter system have become available. However, these agents represent a pharmacologically heterogeneous group and differ in terms of their precise side-effect profile and, possibly, their clinical efficacy. Bupropion, which is thought to act on both the dopamine and norepinephrine (NE) systems, has not been widely used as an antidepressant and has more recently been licensed as adjunctive therapy for smoking cessation. The serotonin-NE reuptake inhibitors venlafaxine and nefazodone, the noradrenergic and specific serotonergic antidepressant mirtazapine, and the selective NE reuptake inhibitor reboxetine (the only truly NE-selective agent available) have all demonstrated efficacy in the treatment of depressive disorders. Evidence is now emerging for their use in the treatment of anxiety and panic disorders. There is some suggestion of a role for noradrenergic agents in other disorders, including attention-deficit/hyperactivity disorder and social phobia. The full range of disorders for which noradrenergic agents can be used remains to be seen and further research in this area is necessary.     

Stimulus control of respondent and operant key pecking: A single key procedure

Pigeons' responses to a uniformly illuminated response key were either reinforced on a variable-interval one-minute schedule of reinforcement or extinguished for one-minute periods. When 1.5 second signals were presented at the beginning of each component, so as to differentially predict reinforcement, the pigeons pecked at the signals, at rates higher than rates during the remainder of the component. When the brief signals were not differentially predictive of reinforcement, pecking in their presence decreased to near zero levels. Similar results were obtained with signals based upon colors and upon line orientations. Changes in rates of (unreinforced) pecking occurred during the signal whether pigeons responded differentially during the remainder of the component or not. Experiment II demonstrated that the presence of the signal correlated with extinction was not necessary for pecking to develop at the signal which preceded the component in which responding was intermittently reinforced. The experiments demonstrated a clear dissociation of respondent control from operant control of a response. In addition, operant behavior was shown to be relatively insensitive to differing rates of reinforcement, as compared to the sensitivity of respondent behavior to differing rates of reinforcement produced by the very same operant behavior.     

Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist

In a recently developed in vitro analog of appetitive classical conditioning of feeding in Aplysia, the unconditioned stimulus (US) was electrical stimulation of the esophageal nerve (En). This nerve is rich in dopamine (DA)-containing processes, which suggests that DA mediates reinforcement during appetitive conditioning. To test this possibility, methylergonovine was used to antagonize DA receptors. Methylergonovine (1 nM) blocked the pairing-specific increase in fictive feeding that is usually induced by in vitro classical conditioning. The present results and previous observation that methylergonovine also blocks the effects of contingent reinforcement in an in vitro analog of appetitive operant conditioning suggest that DA mediates reinforcement for appetitive associative conditioning of feeding in Aplysia.     

ENURESIS CONTROL THROUGH FADING,ESCAPE, AND AVOIDANCE TRAINING

A twin-signal device that provides both escape and avoidance conditioning in enuresis control is described involving a procedure documented by two case studies. In addition, a technique of fading as an adjunct to the process is utilized with one subject. The results indicate that a combination of operant and respondent conditioning involving escape and avoidance training may be an improvement over the more traditional conditioning procedure.     

Depletion of brain norepinephrine with DSP-4 does not alter acquisition or performance of a radial-arm maze task

The acquisition of a radial-arm-maze task was unimpaired following administration of DSP-4, a selective noradrenergic neurotoxin. Maze performance remained unaffected when 5- or 30-min delays were imposed between the fourth and the fifth arm selection. Neurochemical analysis performed 90 days after injection revealed that DSP-4 significantly decreased concentrations of norepinephrine in the hippocampus, cortex, and cerebellum. The regional concentrations of dopamine and serotonin were not affected. These data are consistent with previous reports demonstrating that depletion of brain norepinephrine does not impair spatial learning and memory.     

Changes in cis(Z)-flupentixol-induced dopamine blockade produce contrast effects in rats

Two groups of rats were trained under a 45-sec variable-interval schedule. The magnitude of reinforcement used in each test session alternated daily between one and four 45-mg food pellets, the magnitude of reinforcement available at any time being signalled by lights in the operant chamber. Testing took place over two consecutive 11-day phases. During the first phase one group of rats was injected with 0.06 mg/kg of cis(Z)-flupentixol prior to testing; the other group received vehicle injections. In the second phase drug conditions were reversed. The change in drug conditions between phases produced both positive and negative successive contrast effects, consistent with the hypothesis that dopamine blockade attenuated the hedonic impact of reinforcement. Embedded within each session were two short signalled probe periods during which the reinforcement magnitude was switched to that used on the alternate days. No contrast effects were found during these brief daily probe periods.