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PubMed1993

Dose-dependent discriminative stimulus properties of 8-OH-DPAT.

Separate groups of rats were trained to discriminate either 0.1mg/kg (low dose; L) or 2.5mg/kg (high dose; H) of 8-OH-DPAT from saline, in a standard operant task. Both cues were found to be dose, time and route dependent and generalized completely to the 5-HT(1A) agonists ipsapirone and flesinoxan. Buspirone substituted completely for 8-OH-DPAT in L and partially in H, whereas the 5-HT(1A/1B) receptor agonist eltoprazine substituted completely for 8-OH-DPAT in H but only partially in L. The 5-HT(1A/1B) receptor agonist RU24969, the 5-HT(1B/2C/1A) receptor agonist TFMPP and the 5-HT reuptake blocker fluvoxamine did not completely mimic the effect of 8-OH-DPAT in either L or H and the 5-HT(1A) mixed agonists/antagonists BMY 7378 and NAN-190 produced partial generalization in L, but no generalization in H. In antagonism tests, NAN-190 and BMY 7378 only partially blocked the 8-OH-DPAT cue in both groups. The non-selective 5-HT receptor antagonist methysergide did not completely block the 8-OH-DPAT cue in in L or H. However, in generalization studies, it completely mimicked the 8-OH-DPAT cue in L and produced partial generalization in H. The beta-adrenergic/5-HT(1A/1B) receptor antagonist pindolol completely blocked the 8-OH-DPAT cue in L and H and did not mimic the 8-OH-DPAT cue in either condition. The alpha(2)-adrenoceptor blocker yohimbine substituted fully for the 8-OH-DPAT cue in L and partially in H. Idazoxan did not substitute for the cue of 8-OH-DPAT in H, but produced nearly 80% generalization in L. The dopamine receptor antagonist pimozide neither blocked nor mimicked the cue of 8-OH-DPAT in either group. A number of other drugs (i.e. m-CPP, S(-)-propranolol, DOI, ketanserin, clonidine and apomorphine) were only tested in H. S(-)-Propranolol blocked the 8-OH-DPAT cue but the other compounds produced neither stimulus generalization nor antagonism. The present study demonstrates that the cues produced by the low and the high training dose of 8-OH-DPAT are quantitatively different and mediated by the agonistic activity of 8-OH-DPAT at 5-HT(1A) receptors. Although the results suggest that the 8-OH-DPAT cue (both L and H) is mediated via postsynaptic 5-HT(1A) receptors, the involvement of presynaptic 5-HT(1A) receptors cannot yet be ruled out.

Journal Article↗
PubMed1988

Characterization of the scopolamine stimulus in rats.

The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolamine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.

Animals↗
PubMed1986

Drug preference as a function of arousal and stimulus screening.

The sedating and arousing central nervous system effects of drugs have long been inferred to be a factor in their illicit use and abuse. The present study provides evidence to support this contention; specifically, preference for a particular drug is, in part, a function of arousal-seeking and stimulus-screening characteristics. In general, the results suggest that individuals who prefer central nervous system stimulants tend to have greater arousal-seeking tendencies and lower external stimulus screening ability than those who prefer central nervous system depressants. Opiate preferrers aligned more closely with stimulant preferrers than alcohol groups. Preferrers of hallucinogens were higher in internal stimulus screening than all other drug preference groups. Trait anxiety does not appear to be related to arousal seeking or to preference for arousing or sedating drugs.

Adult↗
PubMedDate not supplied

Is it possible to replace stimulus animals by scent-filled cups in the social discrimination test?

A study in which the rat social discrimination test was refined is described. This test measures social memory by using, in general, juvenile rats as stimulus animals. Rats are offered a first juvenile to investigate (learning trial), and after a specified interval, the rats are offered the same rat and a second juvenile rat to investigate again (retrieval trial). When the rats sniff the second juvenile in the retrieval trial more than the first, social memory for the second juvenile is said to be present. This test is mainly based on scents from the juvenile. Attempts were made to refine the test to reduce the number of animals used, to enhance the scope of the test, and to improve its validity. Firstly, the stimulus animals were replaced by the scent of juveniles, in the form of cups filled with sawdust taken from cages of juvenile rats. Similar results to those in the original test were obtained when using these scents. Furthermore, male and female scents were tested, and showed the same results as for the juvenile scents. Secondly, rats were also given two cups (one scent-filled and one filled with plain sawdust) in the learning trial, to determine which allowed a more-precise delineation of motivational, discriminatory and memory components. Overall, it is possible to replace stimulus animals by scent-filled cups in the social discrimination test, to enhance the scope of the test, and to draw more-valid conclusions with respect to social memory.

Animals↗
PubMed2002

Intensity generalization: physiology and modelling of a neglected topic.

I briefly review empirical data about the generalization of acquired behaviour to novel stimuli, showing that variations in stimulus intensity affect behaviour differently from variations in characteristics such as, for instance, visual shape or sound frequency. I argue that such differences can be seen already in how the sense organs react to changes in intensity compared to changes in other stimulus characteristics. I then evaluate a number of models of generalization with respect to their ability to reproduce intensity generalization. I reach three main conclusions. First, realistic stimulus representations, based on knowledge of the sense organs, are necessary to account for intensity effects. Models employing stimulus representations too remote from the sense organs are unable to reproduce the data. Second, the intuitive notion that generalization is based on similarities between stimuli, possibly modelled as distances in an appropriate representation space, is difficult to reconcile with data about intensity generalization. Third, several simple models, in conjunction with realistic stimulus representations, can account for a wide array of generalization phenomena along both intensity and non-intensity stimulus dimensions. The paper also introduces concepts which may be generally useful to evaluate and compare different models of behaviour.

Animals↗
PubMed2001

The effect of stimulus-response compatibility on cortical motor activation.

Stimulus-response compatibility (SRC) is a general term describing the relationship between a triggering stimulus and its associated motor response. The relationship between stimulus and response can be manipulated at the level of the set of stimulus and response characteristics (set-level) or at the level of the mapping between the individual elements of the stimulus and response sets (element-level). We used functional magnetic resonance imaging (fMRI) to investigate the effects of SRC on functional activation in cortical motor areas. Using behavioral tasks to separately evaluate set- and element-level compatibility, and their interaction, we measured the volume of functional activation in 11 cortical motor areas, in the anterior frontal cortex, and in the superior temporal lobe. Element-level compatibility effects were associated with significant activation in the pre-supplementary motor area (preSMA), the dorsal (PMd) and ventral (PMv) premotor areas, and the parietal areas (inferior, superior, intraparietal sulcus, precuneus). The activation was lateralized to the right hemisphere for most of the areas. Set-level compatibility effects resulted in significant activation in the inferior frontal gyri, anterior cingulate and cingulate motor areas, the PMd, PMv, preSMA, the parietal areas (inferior, superior, intraparietal sulcus, precuneus), and in the superior temporal lobe. Activation in the majority of these areas was lateralized to the left hemisphere. Finally, there was an interaction between set and element-level compatibility in the middle and superior frontal gyri, in an area co-extensive with the dorsolateral prefrontal cortex, suggesting that this area provided the neural substrate for common processing stages, such as working memory and attention, which are engaged when both levels of SRC are manipulated at once.

Adult↗
PubMed1975

Retinal afferents to the pigeon optic tectum: discharge characteristics in response to whole field illumination.

Responses of pigeon retinotectal afferents to changes in whole field illumination are quantitatively analyzed for 313 units recorded in the stratum opticum. One hundred per cent of these units were responsive in unanesthetized birds and 92.9 percent in urethane anesthetized preparations. Of the responsive units, 92.4 percent (anesthetized) and 100 percent (unanesthetized) gave on-responses whose discharge characteristics showed an orderly relationship to stimulus intensity. Following the on-response, discharge generally ceased during sustained illumination. At stimulus termination off-responses frequently occurred, their probability being a function of stimulus intensity and duration. This probability, as well as specific response characteristics, could be predicted to a large extent from on-response characteristics. Anesthesia and level of background illumination predictably affected these response characteristics quantitatively but did not alter them qualitatively. It is hypothesized that with respect to whole field illumination the pigeon's retinotectal afferents constitute a homogeneous population continuously distributed according to threshold for intensity change.

Animals↗
PubMed1991

Onset of tolerance to discriminative stimulus effects of morphine.

Experiments assessed the onset of tolerance to discriminative stimulus effects of morphine in rats treated repeatedly with twice daily doses of 10 mg/kg morphine. Saline and 3.2 mg/kg morphine were established as discriminative stimuli for food-reinforced fixed-ratio performances in several groups of rats, and initial ED50 values were determined for stimulus and rate-altering effects of morphine. To assess onset of tolerance, training was halted and 10 mg/kg doses of morphine were administered repeatedly at 12-h intervals. In separate experiments, ED50 values were redetermined after various treatment periods. One treatment with 10 mg/kg morphine did not alter the ED50 for stimulus effects of morphine, whereas treatment for one or three days increased the ED50 by approximately 2-fold. Comparisons with published data showed even greater tolerance when treatment lasted one or two weeks. Tolerance to stimulus effects of morphine generally was accompanied by tolerance to its rate-decreasing effects. Repeated treatment with morphine also produced cross-tolerance to morphine-like stimulus effects of methadone and buprenorphine. As with morphine itself, greater tolerance developed with longer treatment. These results suggest that tolerance to discriminative stimulus effects of morphine develops gradually, with magnitude of tolerance increasing as a function of treatment duration.

Animals↗
PubMed1989

Electrophysiological and psychophysical testing of vision in glaucoma.

Electrophysiological testing in patients with early glaucoma and in glaucoma suspects reveals defects of central or foveal vision. Most studies suggest that glaucomatous eyes are best separated from normal eyes by use of stimuli with a spatial frequency below the peak of the human contrast sensitivity curve and a relatively high temporal frequency. The stimulus-dependent abnormalities in glaucoma are generally consistent with contrast sensitivity data The stimulus-dependent visual changes are related to the physiology of parallel processing in the primate retinogeniculate pathway.

Aged↗
PubMed1987

Evidence for dopaminergic involvement in tolerance to the discriminative stimulus properties of cocaine.

Rats were trained to discriminate cocaine, 10.0 mg/kg, in a two-lever operant procedure. Dose-effect data for generalization to cocaine and substitution of apomorphine for the cocaine stimulus were determined. Subsequently, training was halted and either apomorphine, 2.5 mg/kg per 8 h, or cocaine, 20 mg/kg per 8 h, was administered for 7-9 days. During chronic administration, the efficacy of cocaine and apomorphine as discriminative stimuli was decreased. These data suggest that dopaminergic mechanisms may mediate tolerance to the discriminative stimulus properties of cocaine.

Animals↗
PubMed1994

Binocular mechanisms for detecting motion-in-depth.

There are in principle at least two binocular sources of information that could be used to determine the motion of an object towards or away from an observer: such motion produces changes in binocular disparities over time and also generates different image velocities in the two eyes. Existing psychophysical and physiological evidence is reviewed. It is concluded that these data are inconclusive concerning whether one or both of these sources of information are used in primate vision. Thresholds were measured for disparity modulations in dynamic (temporally uncorrelated) random dot stereograms (RDS), and for RDS in which the same random dot pattern was used throughout (temporally correlated). Although the first stimulus contains no consistent inter-ocular velocity differences, thresholds were generally slightly lower for this stimulus than for temporally correlated stimuli. Sensitivity to the temporal derivative of disparity is therefore adequate to account for human stereomotion detection. A stimulus was devised in which monocular motion was clearly visible to each eye (with opposite velocities) but in which all disparity changes were beyond the temporal resolution of stereopsis. This produced no sensation of motion-in-depth. Similarly, stimuli beyond the spatial resolution of stereopsis did not support stereomotion detection. These data strongly suggest that stereomotion is primarily detected by means of temporal changes in binocular disparity. We argue that there is no experimental evidence that supports the existence of a mechanism sensitive to inter-ocular velocity differences.

Depth Perception↗
PubMed1991

Preparation time and response complexity effects on stutterers' and nonstutterers' acoustic LRT.

Nonstutterers', mild stutterers', and severe stutterers' acoustic laryngeal reaction times (LRTs) were recorded for isolated vowels and nonpropositional VCV responses in different stimulus conditions governing response preparation. In all stimulus-response conditions severe stutterers produced the longest LRTs, followed in turn by mild stutterers and nonstutterers. The three groups significantly differed from one another in most conditions, but the magnitude of difference between mild and severe stutterers was notably greater than the difference between mild stutterers and nonstutterers. LRT changes as a function of stimulus condition showed that, in general, nonstutterers were best able to use a preparation-facilitating stimulus condition to reduce LRT, and severe stutterers least able to do so. LRT changes as a function of response complexity showed that only nonstutterers produced statistically significant within-group differences. Patterns of LRT change as a combined function of group, stimulus condition, and response type suggest a complex relationship between stutterer severity, preparation time, and type of response complexity. Results illustrate aspects of Goldberg's (1985) model of preparation processes, and support hypotheses that stutterer subgroups show differential preparation deficits along with high motor initiation variability.

Adult↗
PubMed1981

Matching performance and the similarity structure of the stimulus set.

To compare two general approaches toward understanding how objects are classified, this article explores performance in a series of studies that required matching visually presented letters. One general approach has stressed the analysis of details or elements of the input pattern. The other approach has focused on the relationships between the various elements and objects that the observer might expect to occur in the task. In empirical support of the first approach, many researchers have observed that the time it takes a subject to report that two visually presented letters have the same name is less when these letters are physically identical (e.g., A-A) than when they are physically different (e.g., A-a). This relative ease of matching physically identical letters has been attributed to a visual process that matches the letters on the basis of their physical characteristics. In support of the second approach, the studies in this article replicate this finding, but only for data averaged across letter parts. The data from individual letter pairs do not reflect this temporal hierarchy. Individual letter performance for an entire set of letters has not previously been reported, and the importance of analyzing fine structure in data is stressed. It is shown that physical identity matches can be reliably faster or slower than name identity matches. The similarity structure of the total stimulus set reliably predicts which result will occur. Within the limits of the variables studied, this conclusion is shown to be independent of the criterion for the type of match the subject is asked to make (physical identity or name identity) and of the temporal and physical separation of the letters. The readiness with which the presented stimuli can be discriminated from other members of the stimulus set controls performance. For example, as Experiment 1 shows, it is easy or difficult to report o-o as "same" depending on what other letters are used in the task. Lockhead's holistic-discriminability model provides a framework for interpreting these demonstrations that matching performance does not depend only on the stimuli physically present. Performance depends on the similarity or discriminability between the presented stimuli and other stimuli the observers know might be presented.

Discrimination Learning↗
PubMed1988

Discriminative stimulus properties of the isomers of pentobarbital and secobarbital in pigeons.

To date there have been no reports on the discriminative stimulus properties of barbiturate isomers in laboratory animals or man in which the individual isomers were used in the development of the discrimination. To determine what stereospecificity might exist for the stimulus properties of barbiturate isomers, one group of pigeons was trained to discriminate 5 mg/kg of (S)-(-)-pentobarbital from saline and another group was trained to discriminate 8 mg/kg of (R)-(+)-pentobarbital from saline. After responding had stabilized, dose-response curves were determined in both groups for (S)-(-)-pentobarbital (0.3-10 mg/kg), (R)-(+)-pentobarbital (1-17.5 mg/kg), (S)-(-)-secobarbital (0.3-10 mg/kg), (R)-(+)-secobarbital (1-17.5 mg/kg), racemic Na.pentobarbital (1-17.5 mg/kg) and racemic Na.secobarbital (1-17.5 mg/kg). In both groups of pigeons, both isomers of pentobarbital and secobarbital, as well as racemic pentobarbital and racemic secobarbital, showed complete generalization to the training stimulus. For both pentobarbital and secobarbital, the S-(-) isomers showed generalization to the training drug at lower doses than the corresponding R-(+) isomers. No differences were observed in the dose-response curves for the racemic mixtures as a function of the training drug. Thus, no stereoselective differences other than potency could be demonstrated for the stimulus properties of the isomers of pentobarbital and secobarbital.

Animals↗
PubMed1991

Discriminative-stimulus effects of quipazine and l-5-hydroxytryptophan in relation to serotonin binding sites in the pigeon.

The 5-hydroxytryptamine (serotonin; 5-HT) agonists, RU-24969 [5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H-indole, succinate], ipsapirone [2-(4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl)-1,2- benzisothiazol-3-(2H)one-1,1-dioxidehydrochloride], 8-hydroxy-N,N-dipropyl-2-aminotetralin, lysergic acid diethylamide, fenfluramine and N,N-dimethyltryptamine were studied in pigeons trained to discriminate quipazine (1.0 mg/kg) from saline and in pigeons trained to discriminate I-5-HTP (18.0 mg/kg) from saline. Lysergic acid diethylamide, quipazine and fenfluramine generalized to the training stimulus in both groups of pigeons. N,N-dimethyltryptamine generalized to quipazine in all pigeons tested whereas N,N-dimethyltryptamine generalized to I-5-HTP in most pigeons tested. The natural substrate 5-HT and agonists with affinities for the 5-HT1 receptor and its subtypes (8-hydroxy-N,N-dipropyl-2-aminotetralin, ipsapirone, and RU-24969) only generalized in the I-5-HTP-trained pigeons. Equilibrium binding experiments using the ligands [3H]-5-HT and [3H]ketanserin were performed with six areas of pigeon brain and six homologous areas of rat brain. Two populations of 5-HT binding sites were found in brains of both species; one defined by high-affinity binding of [3H]-5-HT and the other defined by high-affinity binding of [3H]ketanserin. Kd values were similar for the two ligands in brains of both species. 5-HT, RU-24969 and ipsapirone displaced [3H]-5-HT but not [3H]ketanserin from pigeon brain membranes. The present study suggests that, in the pigeon, the 5-HT2 receptor might mediate the discriminative-stimulus effects of quipazine, whereas the 5-HT1 receptor might mediate the effects of I-5-HTP.

5-Hydroxytryptophan↗
PubMed1999

Taste qualities of solutions preferred by hamsters.

Molecules of diverse chemical structure are sweet to humans and several lines of evidence (genetic, physiological, behavioral) suggest that there may be distinct sweet perceptual qualities. To address how many perceptual categories these molecules elicit in hamsters (Mesocricetus auratus), we studied patterns of generalization of conditioned taste aversions for seven sweeteners: 100 mM sucrose, 320 mM maltose, 32 mM D-phenylalanine, 3.2 mM sodium saccharin, 16 mM calcium cyclamate, 10 mM dulcin and 32 mM sodium m-nitrobenzene sulfonate. Each stimulus was preferred versus water in two-bottle intake tests and stimulated the chorda tympani nerve. For each of seven experimental groups the conditional stimulus (CS) was a sweetener and for the control group the CS was water. Apomorphine.HCl was injected i.p. after a CS was sampled and, after recovery, test stimuli (TS) were presented for 1 h daily. The intake (ml) of each TS consumed by experimental animals was compared with mean TS intake by the control group. Learned aversions for 18/21 stimulus pairs cross-generalized, resulting in a single cluster of generalization patterns for the seven stimuli. Cross-generalization failures (maltose-cyclamate, maltose-sucrose, cyclamate-NaNBS) may be the consequence of particular stimulus features (e.g. salience, cation taste), rather than the absence of a 'sucrose-like' quality. The results are consistent with a single hamster perceptual quality for a diverse set of chemical structures that are sweet to humans.

Animals↗
PubMed2006

Blocking and pseudoblocking: new control experiments with honeybees.

Prompted by doubts about the adequacy of the various control procedures long used in research on blocking, we repeated some earlier experiments with honeybees that had given the appearance of forward, concurrent, and backward blocking. The new experiments differed from the earlier experiments only in that the target stimulus was omitted during the training and was encountered for the first time in the test. In the new experiments, just as in the earlier experiments, the blocking groups responded less to the target stimulus than did the control groups. The results show that the effects of the different treatments of nontarget stimuli commonly compared in blocking experiments may generalize to the target stimulus and thus affect responding to that stimulus independently of experience with it. Implications for research on blocking in honeybees and other animals are considered.

Animals↗
PubMed1987

Evidence of a central mechanism mediating tolerance to the discriminative stimulus properties of cocaine.

Rats were trained to detect intraperitoneal (IP) administration of cocaine, 10.0 mg/kg, using a two-lever choice discrimination procedure. Following training, cocaine was generalized to the cocaine training stimulus in a dose-dependent manner. Subsequently, bilateral cannulae were implanted in the lateral ventricles in ten animals, and intracerebroventricular (ICV) administration of cocaine was also generalized to the IP training dose in a dose-dependent manner with maximum generalization occurring with 80 micrograms cocaine. After baseline testing, training was halted and cocaine, 20 mg/kg/8-hr, was injected chronically in all rats for 6 days, and then the dose-effect curve for generalization of cocaine was redetermined. Chronic administration of cocaine significantly shifted the dose-effect curve three-fold to the right for both IP and ICV routes of administration. These data suggest that the stimulus properties of cocaine administered centrally are generalized in rats trained by peripheral administration and supports the hypothesis of central mediation of the cocaine stimulus. Also, the comparable shift of the cocaine dose-effect curve following chronic cocaine administration suggests that a central pharmacodynamic mechanism mediates tolerance to the discriminative stimulus properties of cocaine.

Animals↗