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PubMed1993

Discriminative stimulus properties of a new anxiolytic, DN-2327, in rats.

In an operant learning lever-pressing procedure on an FR10 schedule of milk reinforcement, male Wistar rats were trained to discriminate between saline and 3 mg/kg IP DN-2327, a new anxiolytic which acts on benzodiazepine receptors, 3 mg/kg IP diazepam or 15 mg/kg IP pentylenetetrazol (PTZ). More than 80% appropriate lever responding was established after 27, 38 and 44 daily training sessions with DN-2327, diazepam and PTZ, respectively, as the training drug. Although rats trained with DN-2327 dose-dependently generalized to various doses of DN-2327 and diazepam, the cue of DN-2327 was more potent than that of diazepam: ED50 values of DN-2327 and diazepam for stimulus generalization were 0.30 and 0.66 mg/kg, respectively. These animals partially generalized to pentobarbital (1-10 mg/kg) but did not generalize to buspirone (0.1-10 mg/kg). Rats trained with diazepam dose-dependently generalized to various doses of DN-2327, diazepam and pentobarbital with ED50 values of 0.51, 0.47 and 4.5 mg/kg, respectively, but did not generalize to buspirone. In rats trained with PTZ, DN-2327 and diazepam antagonized the discriminative stimulus produced by 15 mg/kg PTZ in a dose-dependent manner with ED50 values of 0.27 and 0.83 mg/kg, respectively, but buspirone neither antagonized nor was able to substitute for the PTZ-induced stimulus. The cue of DN-2327 was antagonized by flumazenil dose-dependently as was that of diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Lorazepam and pentobarbital drug discrimination in baboons: cross-drug generalization and interaction with Ro 15-1788.

Four baboons were trained to discriminate lorazepam (1.0 mg/kg i.m.) and two baboons were trained to discriminate pentobarbital (5.6 mg/kg i.m.) in a two-lever drug discrimination procedure. Food delivery depended on 20 consecutive responses on one lever in sessions preceded by an injection of the training drug and on 20 consecutive responses on the other lever after no drug. All baboons reliably completed 100% of the response runs on the appropriate lever in training sessions. Test sessions were conducted in which a drug dose different from the training dose was injected and 20 consecutive responses on either lever produced food. Drug lever responding occurred after a range of lorazepam and diazepam doses in both lorazepam- and pentobarbital-trained baboons. Drug lever responding also occurred after a range of doses of pentobarbital in the pentobarbital-trained baboons but in only one of the four lorazepam-trained baboons. Ro 15-1788 (0.1-1.0 mg/kg p.o.) antagonized the effect of lorazepam but had no effect on the pentobarbital discriminative stimulus. The asymmetrical generalization with lorazepam and pentobarbital suggests a specificity of discriminative stimulus effects that heretofore have not been documented in drug discrimination experiments with benzodiazepines and barbiturates. The selective antagonism of lorazepam by the benzodiazepine-receptor antagonist Ro 15-1788 suggests that the lorazepam but not the pentobarbital discriminative stimulus is mediated at the benzodiazepine receptor.

Animals↗
PubMed1969

Conditional discrimination learning in the pigeon.

Four pigeons received conditional discrimination training in which reinforcement contingencies were related to specific combinations of color and form, but were unrelated to either color or form considered separately. During discrete-trial training, each response in the presence of two of four color-form displays produced reinforcement and terminated the trial; responding to the other two displays was never reinforced, and each such response prolonged the particular trial on which it occurred. Subsequently, the subjects received multiple-schedule training in which responding to either of the displays previously associated with reinforcement was now reinforced on a variable-interval schedule, and extinction was the schedule again correlated with the other two displays. After differential responding to the stimuli was clearly evident, intensity of the combination displays was changed in subsequent training sessions. Complex stimulus control was generally maintained across variation in intensity, although there were temporary disruptions in performance associated with onset of some of the intensity changes. Finally, a component-stimulus test revealed considerably more responding to the forms than to the colors.

Journal Article↗
PubMed2000

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.

Adaptation, Physiological↗
PubMed1987

Frequency response of spinal Renshaw cells activated by stochastic motor axon stimulation.

In anaesthetized or decerebrate cats, motor axons in lumbosacral ventral roots or hindlimb muscle nerves were stimulated with random trains of brief electrical pulses, and Renshaw cell spike sequences were recorded. Spectral analysis was used to determine the range of linear operation of Renshaw cells, via coherence computations, and to calculate their frequency-dependent gains and phases. The analysis showed that the dynamic behaviour of Renshaw cells was different for different strengths of their synaptic input from motor axons and for different mean stimulus rates. In general, the changes in dynamics associated with variation of these two input parameters followed a common trend. This can be related to the average response of Renshaw cells per stimulus, as assessed by peri-stimulus time histograms. For axons having a strong excitatory effect on a Renshaw cell (as judged from the size of early peri-stimulus time histogram peaks), and for low mean stimulus rates (10-23 pulses per second), the linear range of signal transmission (assessed by coherence computation) was usually very broad (from zero sometimes up to over 100 Hz, but mostly up to 50-100 Hz). Following an initial elevation in the range 2-15 Hz, the gain showed first a rapid decrease with frequency, down to a value which at 30-50 Hz could be a tenth of the gain at lower frequencies (2-15 Hz); it then continued to decline slowly. Otherwise the linear range was narrower and/or the coherence was generally lower; the gain was lower and showed little decline with frequency. The phase curves of Renshaw cells generally showed a low-frequency phase lead (up to roughly 10 Hz) and an increasing phase lag thereabove that was generated in part by the conduction delay. The results show that Renshaw cells can follow, particularly sensitively, inputs in a frequency range encompassing the steady firing rates of many alpha-motoneurons. This range of high gain also covers that of a component of physiological tremor (ca. 6-12 Hz), a basic mechanism of which is probably related to unfused contractions of newly recruited motor units firing in this range. It can therefore be expected that recurrent inhibition via Renshaw cells is especially powerful in this physiologically important range of alpha-motoneuron firing.

Action Potentials↗
PubMed2002

A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities.

Stimulus salience depends both on behavioral context and on other factors such as novelty and frequency of occurrence. The temporo-parietal junction (TPJ) responds preferentially to behaviorally relevant stimuli and is thought to play a general role in detecting salient stimuli. If so, it should respond preferentially to novel or infrequent events, even in a neutral behavioral context. To test this hypothesis, we used event-related functional magnetic resonance imaging (fMRI) to identify brain regions sensitive to the novelty of visual, auditory, and tactile stimuli during passive observation. Cortical regions with a greater response to novel than familiar stimuli across all modalities were identified at two sites in the TPJ region: the supramarginal gyrus (SMG) and superior temporal gyrus. The right inferior frontal gyrus (IFG), right anterior insula, left anterior cingulate cortex (ACC), and left inferior temporal gyrus also showed sensitivity to novelty. The novelty-sensitive TPJ activation in SMG overlaps a region previously identified as sensitive behavioral context. This region may play a general role in identifying salient stimuli, whether the salience is due to the current behavioral context or not. The IFG activation overlaps regions previously identified as responsive to nonnovel sensory events regardless of behavioral context. The IFG may therefore play a general role in stimulus evaluation rather than a specific role in identifying novel stimuli. The ACC activation lies in a region active during complex response-selection tasks, suggesting a general role in detecting and/or planning responses to salient events. A frontal-parietal-cingulate network may serve to identify and evaluate salient sensory stimuli in general.

Acoustic Stimulation↗
PubMedDate not supplied

[The formation in the northern fur seal (Callorhinus ursinus L.) of flexible behavioral programs determined by the structure of the complex visual stimulus].

In Callorhinus ursinus L. generalized rule was elaborated of perception of two-stimuli complex visual stimulus (CVS) presented in random and formed from a set of three differentiated stimuli. The animal was trained to perceive the visual information in linear sequence according to the rule of "reading" from top to bottom and make in conformity with this rule labile two-link visual-motor chains of actions signalled by CVS stimuli. Such behavioural strategies were called by authors ability to operate with CVS structure.

Animals↗
PubMed2006

Statistical learning within and between modalities: pitting abstract against stimulus-specific representations.

When learners encode sequential patterns and generalize their knowledge to novel instances, are they relying on abstract or stimulus-specific representations? Research on artificial grammar learning (AGL) has shown transfer of learning from one stimulus set to another, and such findings have encouraged the view that statistical learning is mediated by abstract representations that are independent of the sense modality or perceptual features of the stimuli. Using a novel modification of the standard AGL paradigm, we obtained data to the contrary. These experiments pitted abstract processing against stimulus-specific learning. The findings show that statistical learning results in knowledge that is stimulus-specific rather than abstract. They show furthermore that learning can proceed in parallel for multiple input streams along separate perceptual dimensions or sense modalities. We conclude that learning sequential structure and generalizing to novel stimuli inherently involve learning mechanisms that are closely tied to the perceptual characteristics of the input.

Association Learning↗
PubMed1985

[Drug discrimination: methodology and current problems].

The purpose of the drug discrimination experiments is, 1) quantitative description of the stimulus properties of drugs, and 2) qualitative description of the stimulus properties, that is, specification of the site of action (central vs peripheral), identification of substance carrying the stimulus property (the drug itself or its metabolites), measurement of similarity to other drugs, and antagonism of the stimulus properties. Feature of drugs as a discriminative stimulus is, 1) change of dose does not mean monotonic change of intensity, that is, different dose may result in different subjective quality, and 2) some drug seems to be a compound stimulus consisting of different stimulus properties, and asymmetric generalization between two drugs and individual differences in generalization tests can be explained in terms of selective stimulus control by different stimulus elements in the compound stimulus. Tolerance, species difference and relationships between the stimulus properties and other drug effects were also discussed.

Animals↗
PubMed1984

Coding responses and the generalization of matching to sample in children.

Two experiments studied the conditions of stimulus control necessary for the generalization of relational matching to sample. Matching required the selection of comparison shapes rotated 90 degrees clockwise from the orientation of the corresponding sample. In Experiment 1, five children were taught to: (a) code the orientations of samples, (b) transform sample codings to account for the 90 degree rotation, and (c) repeat the transformed sample coding response to a comparison. High levels of generalization occurred with a set of novel stimuli for which stable sample-coding responses were initially available. In another novel set, where stable sample-coding responses were not initially available, low levels of generalized matching were recorded. Matching performance improved after stable coding responses were trained. In Experiment 2, two children and three adults were trained in a form of the matching task that produced poor generalization despite the presence of stable sample-coding responses. Retraining to modify the stimulus control exerted by these coding responses produced an immediate improvement in generalized matching to sample. Results suggest that the generalization of matching is dependent on structure of stimulus control that the component responses exert on each other.

Child, Preschool↗
PubMed1992

5-HT3 agonist 2-methylserotonin as a training drug in discrimination studies.

Using a standard two-lever operant procedure, rats were trained to discriminate 5 mg/kg of the 5-HT3 agonist 2-methylserotonin (2-Me 5-HT; ED50 = 2.6 mg/kg) from saline using a VI 15-s schedule of reinforcement. The 2-Me 5-HT stimulus did not generalize to the 5-HT1/5-HT2 agonist 5-methoxy-N,N-dimethyltryptamine, but did generalize to the new 5-HT3 agonist 1-(m-chlorophenyl)biguanide (ED50 = 1.6 mg kg). The 5-HT3 antagonist ICS 205-930 potently antagonized the 2-Me 5-HT stimulus (ID50 = 0.001 mg/kg), whereas its quaternary amine analog, which does not readily penetrate the blood-brain barrier, failed to completely antagonize the 2-Me 5-HT stimulus at a 10,000-fold higher dose. The results of the present investigation show that 2-Me 5-HT serves as a discriminative stimulus in rats when paired with saline and suggest that its stimulus properties are likely mediated via a central 5-HT3 mechanism. As such, this is the first demonstration that a 5-HT3 agonist can be used as a training drug in drug discrimination studies.

Animals↗
PubMed1997

Bistable biochemical switching and the control of the events of the cell cycle.

Some of the events of the cell cycle appear to be triggered by a bistable mechanism. A bistable biochemical system can respond to a small, slow signal and is carried by positive feedback from one stable steady state directly to another, in an all-or-none manner. Slow or subthreshold stimuli do not cause accommodation or loss of excitability. Switching is not readily reversible by removing the stimulus, i.e. there is hysteresis: reversal generally requires a stronger, opposite stimulus. Biochemically, bistable biochemical switching requires positive feedback, and mechanisms for stabilizing the system against premature activation and for destabilization in response to a biological signal. Three bistable biochemical models, all suggested by reported experimental observations, are described and analysed. These models suggest that a titratable inhibitor may play an important part in bistable switching, because the end-point of titration can form a natural threshold for enhancement of positive feedback.

Carrier Proteins↗
PubMed1999

Disruption of the discriminative stimulus effects of S(+)-3,4-methylenedioxymethamphetamine (MDMA) by (+/-)-MDMA neurotoxicity: protection by fluoxetine.

This study utilized drug discrimination procedures to assess the functional consequences of (+/-)-3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin depletion, and to determine whether concomitant injections of fluoxetine averted these effects. Twelve male Sprague-Dawley rats were trained to discriminate S(+)-MDMA (1.5 mg/kg, s.c.) from saline in a two-lever, water-reinforced operant procedure. After dose generalization tests were completed, training was suspended, and subjects were administered saline injections twice daily for four days. Ten days later, tests were conducted with S(+)-MDMA (1.5 mg/kg) and saline, to ascertain that discriminative stimulus control was maintained in the absence of training over a two-week period. All subjects received two additional weeks of training. Subsequently, (+/-)-MDMA (20 mg/kg, s.c.) was administered twice daily for four days, concomitantly with either 5.0 mg/kg fluoxetine (FLX) or saline (SAL) injections, and stimulus generalization tests with S(+)-MDMA and SAL were conducted after ten days. In the rats administered (+/-)-MDMA + SAL injections, S(+)-MDMA-appropriate responding dropped from 99.24% to 44.99% during S(+)-MDMA generalization tests, and rose from 2.78% to 22.14% during SAL generalization tests. This disruption did not occur, however, in rats administered the combination of (+/-)-MDMA and FLX injections. Subsequent training reestablished discriminative stimulus control by S(+)-MDMA in the (+/-)-MDMA + SAL-treated rats. Postmortem neurochemical assays indicated that 5-HT levels were significantly reduced in the prefrontal cortices of rats given (+/-)-MDMA + SAL, compared to both drug-naive control rats and (+/-)-MDMA + FLX-treated rats. 5-HIAA levels were significantly lower in the prefrontal cortices of both (+/-)-MDMA + SAL-treated rats and (+/-)-MDMA + FLX-treated rats, relative to control. These results support previous findings that fluoxetine protects against (+/-)-MDMA-induced 5-HT depletion. Moreover, this study demonstrated that drug discrimination is a sensitive assay in which to examine behavioral correlates of (+/-)-MDMA-induced serotonergic deficits, and the protection against these deficits by fluoxetine.

Animals↗
PubMed2006

Visual processing and infant ocular Latencies in the overlap paradigm.

Young infants have repeatedly been shown to be slower than older infants to shift fixation from a midline stimulus to a peripheral stimulus. This is generally thought to reflect maturation of the neural substrates that mediate the disengagement of attention, but this developmental difference may also be attributable to young infants' slower processing of the midline stimulus. This possibility was tested with 3- and 7-month-old infants in 2 experiments in which the degree of familiarity of the midline stimulus was manipulated across repeated trials. The results of these experiments demonstrated that the processing of midline content does affect infants' ocular latencies to a peripheral stimulus but that developmental differences in such processing do not account for developmental differences in disengagement seen across the 1st year.

Age Factors↗
PubMed1996

Recognition of visual stimuli from multiple neuronal activity in monkey visual cortex.

Response patterns recorded with 30 microelectrodes from area 17 of anaesthetized monkeys are analysed. A proportion of the patterns are used to define prototype response patterns. These in turn are used to recognize the stimulus from further non-averaged response patterns. In comparison, recognition by a feedforward 'neural network' is much slower, and slightly inferior. The excitation time structure, with a resolution of about 20 ms, is found to contribute strongly to the recognition. There is some inter-ocular recognition for oriented moving bars, and for on and off phases of switched lights, but none for colours. Generalizations over some stimulus parameters (i.e. cases of confusion) are examined: If small jerking shapes are incorrectly recognized, in general the jerk direction often is the correct one. The onset of a response can most easily be found by determining the dissimilarity relative to spontaneous activity in a sliding window.

Animals↗
PubMed1989

Identifying stimuli in the natural environment that control verbal responses.

When a learner is taught a new response, the stimuli that influence its display often are unknown. These stimuli alter the probability of occurrence of the response. That is, when they are present, the response occurs; when they are absent, it does not occur. By identifying the stimuli that influence the probability of newly acquired responses, interventionists may program for their generalization more effectively and efficiently. In the present study, 2 students who were moderately retarded were taught to label a coin. Eight environmental stimuli that were present during training were identified. The effect of each stimulus on the occurrence of the response was assessed prior to and after training by presenting the remaining seven stimuli and altering only the target stimulus. The results demonstrated that by altering one stimulus at a time, responding continued uninterrupted. For 1 of the 2 learners, however, responding was disrupted by altering two stimuli simultaneously. The implications of these findings are discussed in terms of stimulus control and generalization.

Child↗