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Results for “Generalization, Stimulus”

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PubMed1995

Effects of the NMDA antagonist, dizocilpine, in various drug discriminations: characterization of intermediate levels of drug lever selection.

In each of different groups of rats trained to discriminate either 8-OH-DPAT, DOI, d-amphetamine, cocaine, chlordiazepoide or ethanol from saline, dizocilpine produced maximum percentages of drug lever (DL) selection that were intermediate between those produced by the training conditions. Dizocilpine also decreased DL selection produced by the training dose in each of the discriminations, except in ethanol-trained rats. In all discriminations, with the exception of ethanol-trained rats, the intermediate levels of DL, selection produced by dizocilpine were associated with increased FRF values (sum of the responses made on either lever before the first reinforcement occurred), increased lever selection latencies, and increased responding on the nonselected lever. At doses that, in general, had effects on response rate similar to those of dizocilpine, intermediate levels of DL selection were produced by BMY 7378 in 8-OH-DPAT-trained rats, by WY 50,324 in DOI-trained rats, by (-)-3-PPP in d-amphetamine- and in cocaine-trained rats, by alpidem in chlordiazepoxide-trained rats, and by PCP in ethanol-trained rats. The intermediate levels of DL selection produced by these latter drugs were not associated with simultaneous increases of FRF values, selection latencies, and responding on the nonselected lever. The results suggest that dizocilpine produces intermediate levels of drug-appropriate responding through the behavioral mechanism of partial generalization only in ethanol-trained rats; in all other discriminations examined here, the effects of dizocilpine appear to involve (1) pharmacological effects that differ from those of the training drug, and (2) behavioral mechanisms that are unrelated to stimulus generalization. The differentiation of partial generalization and other mechanisms whereby intermediate responding can occur in the drug discrimination paradigm requires analyses that are more detailed than those commonly used in drug discrimination research.

Journal Article↗

PubMed1996

Stimulus uncertainty and speaker normalization processes in the perception of nasal consonants.

Previous research has noted a reduction in perceptual identification performance when the speaker varies from stimulus to stimulus and has interpreted this finding as an effect of a normalization process that compensates for variability in the physical content of the speech signal. The purpose of the present investigation was to examine whether the physical variability introduced by this experimental design can result in general stimulus uncertainty effects that extend beyond the realm of traditional delineations of normalization processes. The stimuli were short segments taken from nasal consonant + vowel syllables produced by 1 male adult, 1 female adult, and 2 children. Segments of 25 and 50 ms duration were edited from the nasal murmur and the onset of the vowel. The stimuli were ordered according to four variability conditions and presented to listeners for place of articulation identification. The results showed that identification was significantly reduced when variability affected either speaker identity or segment type. Further analyses revealed that segment variability impaired perception of all segment types approximately equally, but that the 50-ms vowel segments were selectively spared in the speaker variability condition. These findings indicate that general uncertainty effects should be considered in speech perception experiments, and that dynamic properties of speech are particularly important in the perceptual compensation for speaker variability.

Adult↗

PubMed1987

Behavioral effects of several new anxiolytics and putative anxiolytics.

The behavioral effects of several new anxiolytics and putative anxiolytics were evaluated in two tests sensitive for anxiolytic activity. In the first test, rats were trained to lever-respond for sweetened milk under a multiple variable-interval fixed-ratio (VI-FR) schedule of reinforcement. In the FR component a brief electric shock coincided with the presentation of reward (i.e. conflict procedure). Treatment of these rats with diazepam, tracazolate, CGS-9896, and the pyrimidinylpiperazine derivatives buspirone, gepirone and ipsapirone (TVX Q 7821) significantly increased responding that was suppressed by foot-shock. A common metabolite of the pyrimidinylpiperazines, l-PP, had no affect on punished responding. A second group of rats was trained to discriminate diazepam from saline using a two-lever operant choice procedure. Diazepam-stimulus generalization occurred to CGS-9896, CL 218,872, zopiclone and tracazolate, but not to buspirone, gepirone, ipsapirone or l-PP. It was concluded that while all of the new compounds examined appear to share an anxiolytic effect as demonstrated by their activity in the conflict procedure, the pyrimidinylpiperazine agents do not share discriminative stimulus properties which are common to drugs which act via the benzodiazepine receptor.

Animals↗

PubMedDate not supplied

Different parameters support generalization and discrimination learning in Drosophila at the flight simulator.

We have used a genetically tractable model system, the fruit fly Drosophila melanogaster to study the interdependence between sensory processing and associative processing on learning performance. We investigated the influence of variations in the physical and predictive properties of color stimuli in several different operant-conditioning procedures on the subsequent learning performance. These procedures included context and stimulus generalization as well as color, compound, and conditional discrimination (colors and patterns). A surprisingly complex dependence of the learning performance on the colors' physical and predictive properties emerged, which was clarified by taking into account the fly-subjective perception of the color stimuli. Based on estimates of the stimuli's color and brightness values, we propose that the different tasks are supported by different parameters of the color stimuli; generalization occurs only if the chromaticity is sufficiently similar, whereas discrimination learning relies on brightness differences.

Animals↗

PubMedDate not supplied

Neuron types, receptors, behavior, and taste quality.

Neurophysiological studies on chorda tympani (CT) single fibers and behavioral studies on generalization of learned aversions in hamsters (Mesocricetus auratus) are reviewed. The work on hamsters is compared to work on other species, including the laboratory rat and several primate species, including humans. This body of data demonstrates associations between response profiles of physiologically defined specialist CT neurons and behavioral stimulus generalizations on one hand, and characteristics of putative taste receptors, on the other. Response profiles of generalist CT neurons are similarly associated with receptor characteristics, but are not associated with specific behavioral discriminations. The associations of peripheral nerve data with both receptor and behavior strongly suggest specific codes for "sucrose-like" and "NaCl-like" taste qualities. Definitive conclusions regarding "patterns" or "labeled lines" requires an understanding of mechanisms of central neural processing of the several specialist and generalist taste-afferent inputs.

Animals↗

PubMed1977

Tolerance to morphine-produced discriminative stimuli and analgesia.

Male hooded rats were trained in Skinner boxes to press one lever after a morphine injection (10 mg/kg) and another lever after a saline injection (1 ml/kg) on an FR 10 schedule of food reinforcement. After the drug discrimination was well established, the rats were tested for stimulus generalization at different doses of morphine, followed by assessment of tail withdrawal latency as a measure of analgesia. Subjects were then administered increasing doses of morphine sulphate to induce an increased level of tolerance. New dose-response curves indicated that tolerance developed to the morphine-induced discriminative stimulus, and to the analgesic action of morphine, but doses of morphine that failed to cause detectable analgesia still produced a pronounced discriminative stimulus.

Analgesia↗

PubMed1985

Sedation and the stimulus properties of antihistamines.

A group of six rats was trained to discriminate the effects of diphenhydramine (10 mg/kg; 30 min pretreatment time) and saline in a two-lever choice task using a fixed ratio schedule of water reinforcement. Stimulus control was assumed to be present when 80% or more of the first ten responses were appropriate for the treatment condition on each of five consecutive days. Diphenhydramine established stimulus control in each of the subjects. The mean number of sessions prior to the onset of criterion performance was 26 (standard error = 7). A second group of six rats was similarly trained with chlorpheniramine (10 mg/kg; 30 min pretreatment time) and saline. Four of the group reached criterion performance in a mean of 56 sessions (SE = 7). The diphenhydramine stimulus generalized completely to promethazine, azatidine, and chlorpheniramine. In rats trained with chlorpheniramine, only promethazine and azatidine substituted completely while diphenhydramine yielded intermediate results, i.e., significantly different from both training conditions. It is concluded that the relative propensity of antihistamines to induce sedation in humans is not correlated with distinctive stimulus properties in the rat.

Animals↗

PubMed1986

Comparative discriminative stimulus properties of dl-cathinone, d-amphetamine, and cocaine in rats.

The discriminative stimulus properties of dl-cathinone (dl-CAT), d-amphetamine (d-A), and cocaine (COC) were compared and effects of haloperidol pretreatment on these properties were studied in rats. The ED50's of each drug were also determined. Stimulus generalization (i.e., greater than 75% of responses occurring on the drug lever) occurred with each of the three training drugs to all three test drugs. The degree of generalization was less between d-amphetamine and dl-cathinone than between d-amphetamine and cocaine or between cocaine and dl-cathinone. No significant differences were observed among the ED50's of each test drug obtained in all three training groups. Pretreatment with haloperidol failed to alter the stimulus properties of dl-cathinone. Haloperidol administration did partially antagonize the stimulus complex induced by d-amphetamine and cocaine. It is concluded that all three agents share somewhat similar but not identical, stimulus properties. The stimulus properties of the training dose of d-amphetamine may be somewhat different from those of dl-cathinone and may be more dependent on functional dopaminergic pathways.

Alkaloids↗

PubMedDate not supplied

Discriminative stimulus properties of alpha-ethyltryptamine optical isomers.

alpha-Ethyltryptamine (alpha-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alpha-ET substituted for MDMA. These previous studies employed racemic alpha-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of alpha-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. (-)alpha-ET (ED(50)=7.8 mg/kg), but not (+)alpha-ET (maximum of 53% drug-appropriate responding), substituted for (+)amphetamine, whereas (+)alpha-ET (ED(50)=2.7 mg/kg), but not (-)alpha-ET (maximum of 33% drug-appropriate responding), substituted for DOM. Both optical isomers of alpha-ET substituted for PMMA and MDMA with ED(50) values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for (-)alpha-ET and (+)alpha-ET, respectively. The results of this investigation suggest that both optical isomers of alpha-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of alpha-ET resides primarily with its (-)isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer.

Animals↗

PubMed1993

Pseudorandom binary sequence stimulation applied to the visual evoked response. Normative data and a comparative study with pattern and flash stimulation.

The investigation of patients who are unable to fixate the pattern visual stimulus generally requires the use of diffuse flash stimulation to elicit the visual evoked response. However, by comparison with pattern, flash stimulation has proved relatively insensitive in identifying lesions of the visual pathway. We investigated a more complex method of flash stimulation. A pseudorandom binary sequence has been used to generate the diffuse visual evoked response stimulus. The pseudorandom binary sequence, rather than producing a single flash, switches in a pseudorandom fashion between two levels of illumination. The result is a diffuse visual stimulus approximating band-limited white noise. The series is periodic, enabling signal averaging to be performed. By applying the methods of random signal analysis, the impulse or transient response of the visual pathway can be determined. Our normal pseudo-random binary sequence visual evoked response impulse function, derived from 29 normal subjects, had the morphologic characteristics of the conventional flash visual evoked response and a major positive component (P100), whose latency mean and standard deviation closely matched that of our normative pattern visual evoked response. However, the P100 amplitude standard deviation was significantly greater than that produced by conventional pattern and flash stimulation. We investigated 140 patients by means of pattern, flash and pseudorandom binary sequence stimulation. The pseudorandom binary sequence visual evoked response proved to be almost 12 times more effective than flash visual evoked response in detecting lesions of the visual system.

Adolescent↗

PubMed2006

Recency effects as a window to generalization: separating decisional and perceptual sequential effects in category learning.

Accounts of learning and generalization typically focus on factors related to lasting changes in representation (i.e., long-term memory). The authors present evidence that shorter term effects also play a critical role in determining performance and that these recency effects can be subdivided into perceptual and decisional components. Experimental results based on a probabilistic category structure show that the previous stimulus exerts a contrastive effect on the current percept (perceptual recency) and that responses are biased toward or away from the previous feedback, depending on the similarity between successive stimuli (decisional recency). A method for assessing these recency effects is presented that clarifies open questions regarding stimulus generalization and perceptual contrast effects in categorization and in other domains.

Attention↗

PubMed2004

Stimulus effects of three sulfur-containing psychoactive agents.

Two agents gaining popularity on the illicit drug market are the phenylalkylamines 4-MTA and 2C-T-7 [or 1-(4-methylthiophenyl)-2-aminopropane and 2-(2,5-dimethoxy-4-n-propylthiophenyl)-1-aminoethane, respectively]. At this time, there exists a paucity of information on the behavioral actions of these sulfur-containing agents. The present investigation examined these agents, and the N-monomethyl analog of 4-MTA (i.e., 4-MTMA), in tests of stimulus generalization (substitution) using a two-lever drug discrimination task with groups of rats trained to discriminate either the hallucinogen DOM [1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane], the stimulant cocaine, or the empathogen MDMA from vehicle. 4-MTA and its N-monomethyl analog 4-MTMA (ED50 = 0.8 mg/kg in both cases) substituted only for the MDMA stimulus, whereas 2C-T-7 (ED50 = 0.8 mg/kg) substituted only for the DOM stimulus. Thus, at the doses examined, 4-MTA and 4-MTMA appear to be MDMA-like agents, and 2C-T-7 seems best classified as a DOM-like hallucinogen. These results provide additional data that extend the structure-activity relationships of phenylalkylamines and that are consistent with what little is currently known about the action of 4-MTA and 2C-T-7 in humans.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1983

Three-choice drug discrimination: phencyclidine-like stimulus effects of opioids.

To assess the commonalities and differences in the discriminative stimulus properties of phencyclidine (PCP) and psychotomimetic opioids, rats were trained to discriminate PCP (2.0 mg/kg), cyclazocine (1.0 mg/kg), and saline in a three-choice discrete-trial avoidance paradigm. Stimulus control of behavior, defined as the reliable completion of 18 trials of a 20-trial session on the appropriate choice lever after administration of PCP, cyclazocine, or saline, was established in an average of 157 sessions. In tests of stimulus generalization, SKF-10,047 and dextrorphan engendered lever choices appropriate to both PCP and cyclazocine, sometimes in the same animal and at the same dose. The rats responded almost exclusively on the PCP-appropriate lever after ketamine and on the saline lever after morphine and d-amphetamine, indicating pharmacologic specificity. Naltrexone, in doses that had little effect on stimulus control of behavior by PCP, completely blocked cyclazocine-like stimulus control. Decreases in cyclazocine choices in the presence of naltrexone were associated with increases in PCP choices. These results support conclusions derived from two-choice procedures that psychotomimetic opioids have PCP-like stimulus effects, and provide direct evidence that these effects of cyclazocine are mediated by a component of action insensitive to an opiate antagonist.

Animals↗

PubMed2002

Effect of PMA optical isomers and 4-MTA in PMMA-trained rats.

1-(4-Methoxyphenyl)-2-aminopropane (PMA) and its sulfur analog, 1-(4-methylthiophenyl)-2-aminopropane (4-MTA), have been misrepresented as the controlled substance analog, N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; "Ecstasy"). Because MDMA has been shown to produce both amphetamine-like and N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA)-like stimulus effects in rats, we examined S(+)PMA, R(-)PMA and 4-MTA in rats trained to discriminate either PMMA (1.25 mg/kg) or (+)amphetamine (1.0 mg/kg) from saline vehicle. The sulfur analog of PMMA (i.e., 4-MTMA) was also examined. The PMMA stimulus generalized to R(-)PMA (ED50=0.4 mg/kg), whereas S(+)PMA produced a maximum of 72% PMMA-appropriate responding. 4-MTA (ED50=0.3 mg/kg) also substituted for PMMA, but 4-MTMA produced a maximum of only 36% PMMA-appropriate responding. None of the four agents substituted for (+)amphetamine. Hence, like MDMA, R(-)PMA and 4-MTA are capable of producing PMMA stimulus effects in rats, but unlike MDMA, neither agent substituted for (+)amphetamine.

Animals↗

PubMedDate not supplied

Role of serotonin in the discriminative stimulus properties of mescaline.

Rats were trained to discriminate intraperitoneally administered mescaline from saline in a two-lever operant chamber for food reinforcement. Reward was contingent upon responses made greater than 15 sec apart (DRL-15) on the appropriate lever paired with either drug or saline administration. Following the establishment of discriminative response control by mescaline, the animals were tested for stimulus generalization produced by mescaline after: (a) blockade of periphreral and central serotonin (5-HT) receptors with cinanserin, methysergide, or cyproheptadine; (b) blockade of peripheral 5-HT receptors with xylamidine tosylate; and (c) depletion of brain 5-HT with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA). The results show that all three central 5-HT antagonists greatly reduced the discriminability of mescaline while the peripheral antagonist, xylamidine tosylate, was without effect. Furthermore, these agents at the doses employed did not effect the discriminability of saline. Depletion of 5-HT with PCPA potentiated the effects of a sub-threshold dose of mescaline and slightly reduced the discriminability of saline. The results indicate that mescaline produces its discriminative stimulus properties by directly stimulating central serotonergic receptors.

Animals↗

PubMed2002

Reevaluation of PNU-99194A discriminative stimulus effects: potentiation by both a D2 antagonist and a D3/D2 agonist.

This study evaluated the relative importance of D(3) receptor antagonism in the discriminative stimulus effects of the putative D(3) receptor antagonist PNU-99194A. Eight male Sprague-Dawley rats were trained to discriminate PNU-99194A (10 mg/kg sc) from vehicle in a two-choice drug discrimination procedure under a FR 20 schedule of food reinforcement. The selective D(3) antagonists PD 152255 and S14297 were examined for stimulus generalization. The D(2) antagonist haloperidol and the D(2)/D(3) receptor agonist (+)-7-OH-DPAT were also assessed for antagonism of PNU-99194A discrimination. PD 152255 (1.0-3.0 mg/kg) engendered no generalization to PNU-99194A. Due to its markedly rate-suppressive effects, PD 152255 could not be tested at higher doses. S-14297 produced partial substitution (66%) for PNU-99194A at both 3.0 and 8.0 mg/kg. Neither haloperidol nor (+)-7-OH-DPAT blocked the discrimination of PNU-99194A and, surprisingly, actually appeared to potentiate its effects. These data, along with other recent findings, suggest that the discriminative stimulus effects of PNU-99194A appear to involve complex pharmacological actions and are not solely mediated by D(3) receptor antagonism.

Animals↗

PubMed1987

Separation of the response rate and discriminative stimulus effects of phencyclidine: training dose as a factor in phencyclidine-saline discrimination.

The training dose was progressively reduced (faded) using rats in a drug discrimination task in order to determine whether the discriminative stimulus effects of phencyclidine HCI (PCP) were separable from its response rate effects. Rats were initially trained to discriminate PCP from saline in a two-lever food-reinforced operant discrimination procedure. After initial training at 3.0 mg/kg, the rats were subsequently retrained at 1.5, 0.75 and 0.375 mg/kg. Stimulus generalization testing followed training at each training dose. Although discriminative control was developed by lower doses of PCP during the fading procedures, control by previously effective higher doses was not diminished. The number of training sessions required before reaching criterion levels of performance and the number of errors during training (i.e., incorrect lever selections) increased with decreases in training dose. The results indicated that fading of the training dose of PCP caused marked parallel shifts in the dose-effect curves for PCP's discriminative stimulus effects although its response rate effects were left unaffected. The ED50 for PCP's discriminative stimulus effects decreased with decreases in training dose although the ratio of the ED50 to the training dose remained relatively constant. The ED50 for the response rate effects, however, remained relatively constant with decreases in training dose, and the ratio of the ED50 to the training dose markedly increased. It was concluded that the discriminative stimulus and the response rate effects of PCP are separable and, hence are under control by different determinants.

Animals↗

PubMed1981

Factors regulating drug cue sensitivity: the effect of frustrative non-reward in fentanyl-saline discrimination.

In this study, rats were trained to discriminate 0.04 mg/kg of fentanyl from saline in two-lever food-reinforced procedure. The study examined the effects of a manipulation of reinforcement (i.e. frustrative non-reward; FNR) on several characteristics of fentanyl-saline discrimination. It was found that asymmetrical FNR in either saline or drug sessions retarded the acquisition of the discrimination and codetermined response bias; symmetrical FNR in both types of sessions had no effect. Asymmetrical FNR in saline sessions steepened the slope of the generalization of fentanyl, but also of morphine and sufentanil; asymmetrical FNR in drug sessions flattened the gradient's slope. Symmetrical FNR had effects on slope which were similar to those of asymmetrical FNR in saline sessions. Both symmetrical and asymmetrical FNR also appeared to affect the ED50-value of different agonists, and the ED50-value of naloxone in antagonizing 0.04 mg/kg of fentanyl. It thus appears that reinforcement plays a major role in the acquisition of fentanyl-saline discrimination and in the quantitative characteristics of the stimulus generalization gradient of fentanyl and other agonists. It is also suggested that the training drug itself may interact with the effects of FNR on its own gradient.

Animals↗