S-16924, a novel, potential antipsychotic with marked serotonin1A agonist properties. IV. A drug discrimination comparison with clozapine.
(1/150)
The novel benzodioxopyrrolidine (S-16924) displays a clozapine-like profile of interaction with multiple monoaminergic receptors, in addition to potent agonist activity at serotonin (5-HT)1A receptors. S-16924 (2.5 mg/kg i.p.) and clozapine (5.0 mg/kg i.p.) generated robust discriminative stimuli (DS) and displayed full mutual generalization. The D4 antagonists L-745,870 and S-18126, the D1/D5 antagonist SCH-39166, and the D3 antagonist S-14297 showed at most partial generalization to S-16924 and clozapine. The D2/D3 antagonist raclopride fully generalized to S-16924, but only partially generalized to clozapine. The 5-HT2A antagonist MDL-100, 907 fully generalized to S-16924 and two further 5-HT2A antagonists, fananserin and SR-46349, showed partial generalization. However, MDL-100,907, fananserin, and SR-46349 showed less pronounced generalization to clozapine. Similarly, the 5-HT2C antagonists SB-200,646 and SB-206,553 more markedly generalized to S-16924 than to clozapine. The 5-HT1A receptor agonist (+/-)-8-dihydroxy-2-(di-n-propylamino) tetralin generalized fully to S-16924 but not to clozapine. Full generalization was obtained to both S-16924 and clozapine for the clozapine congeners, olanzapine and quetiapine. In distinction, the benzisoxazole, risperidone, and the phenylindole, sertindole, weakly generalized to S-16924 and clozapine. However, the benzisoxazole ziprasidone, which possesses 5-HT1A agonist properties, generalized fully to S-16924 but not to clozapine. Finally, the muscarinic antagonist scopolamine generalized fully to clozapine and partially to S-16924. In conclusion, S-16924 and clozapine display both communalities and differences in their "compound" DS; this likely reflects their respective complex patterns of interaction with multiple monoaminergic receptors. Although no specific receptor was identified as underlying the clozapine DS, 5-HT1A agonist as well as D2 and 5-HT2A/2C antagonist properties contribute to the S-16924 DS. (+info)
Equivalence class establishment, expansion, and modification in preschool children.
(2/150)
Preschool children were taught four two-choice match-to-sample conditional discriminations with 10 arbitrary visual stimuli. For 6 participants, 2 of the 10 stimuli served as the sample, or conditional, stimuli in all discriminations. For 5 additional participants, the same pair of stimuli served as the discriminative, or comparison, stimuli in all discriminations. Equivalence classes were established with more participants in the latter group, replicating prior research with participants with retardation. Four participants, in whom equivalence classes were established and who were available for further participation, were exposed to new conditional discriminations without trial-by-trial feedback and involving some novel and some familiar stimuli. Consistent conditional responding was observed, and tests for inclusion of the novel stimuli in the original classes showed class expansion. Training to reverse the unreinforced conditional performances produced a reversal of class membership in 3 of 4 participants, an outcome not consistent with other studies. The results are discussed with respect to the interaction of class structure and size. (+info)
Generalization of habituation and intrinsic sensitization in the leech.
(3/150)
Using the shortening reflex of the medicinal leech Hirudo medicinalis we examined stimulus generalization of habituation learning. Preparations received mechanosensory stimulus at two positions on the leech body wall, one site used to carry out habituation training and a second novel site to test for generalization of habituation. After training, the specific mechanosensory neurons activated by each stimulus were assessed using intracellular recordings. As expected, the closer the two sites were to each other, the greater the degree of generalization of habituation at the novel site and the more sensory cells were shared. However, a form of behavioral facilitation was observed at the trained site that resembled behavioral sensitization, but differed from the standard sensitization process in several respects. (1) Facilitation was induced by stimulation of the novel site before habituation training at the trained site, although the stimulus intensity at the novel site was equivalent to the training stimuli and was not the strong, noxious stimuli that normally induce sensitization. (2) The magnitude of the facilitating effect was proportional to the proximity of the novel and trained stimulation sites. (3) Although behavior at the trained site was facilitated, behavior at the novel site was habituated, indicating that the induced behavioral facilitation did not generalize throughout the animal, as normally occurs during sensitization, but was limited to a single stimulus-response pathway. (+info)
Mechanisms of generalization in perceptual learning.
(4/150)
Learning in many visual perceptual tasks has been shown to be specific to practiced stimuli, while new stimuli have to be learned from scratch. Here we demonstrate generalization using a novel paradigm in motion discrimination where learning has been previously shown to be specific. We trained subjects to discriminate directions of moving dots, and verified the previous results that learning does not transfer from a trained direction to a new one. However, by tracking the subjects' performance across time in the new direction, we found that their speed of learning doubled. Therefore, we found generalization in a task previously considered too difficult to generalize. We also replicated, in a second experiment, transfer following training with 'easy' stimuli, when the difference between motion directions is enlarged. In a third experiment we found a new mode of generalization: after mastering the task with an easy stimulus, subjects who have practiced briefly to discriminate the easy stimulus in a new direction generalize to a difficult stimulus in that direction. This generalization depends on both the mastering and the brief practice. The specificity of perceptual learning and the dichotomy between learning of 'easy' versus 'difficult' tasks have been assumed to involve different learning processes at different cortical areas. Here we show how to interpret these results in terms of signal detection theory. With the assumption of limited computational capacity, we obtain the observed phenomena--direct transfer and acceleration of learning--for increasing levels of task difficulty. Human perceptual learning and generalization, therefore, concur with a generic discrimination system. (+info)
Trajectory encoding in the hippocampus and entorhinal cortex.
(5/150)
We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of rats to investigate the role of these structures in navigation and memory representation. Our results revealed two novel phenomena: first, many cells in CA1 and the EC fired at significantly different rates when the animal was in the same position depending on where the animal had come from or where it was going. Second, cells in deep layers of the EC, the targets of hippocampal outputs, appeared to represent the similarities between locations on spatially distinct trajectories through the environment. Our findings suggest that the hippocampus represents the animal's position in the context of a trajectory through space and that the EC represents regularities across different trajectories that could allow for generalization across experiences. (+info)
Colour categorization by domestic chicks.
(6/150)
Spectral stimuli form a physical continuum, which humans divide into discrete non-overlapping regions or categories that are designated by colour names. Little is known about whether non-verbal animals form categories on stimulus continua, but work in psychology and artificial intelligence provides models for stimulus generalization and categorization. We compare predictions of such models to the way poultry chicks (Gallus gallus) generalize to novel stimuli following appetitive training to either one or two colours. If the two training colours are (to human eyes) red and greenish-yellow or green and blue, chicks prefer intermediates, i.e. orange rather than red or yellow and turquoise rather than green or blue. The level of preference for intermediate colours implies that the chicks interpolate between the training stimuli. However, they do not extrapolate beyond the limits set by the training stimuli, at least for red and yellow training colours. Similarly, chicks trained to red and blue generalize to purple, but they do not generalize across grey after training to the complementary colours yellow and blue. These results are consistent with a modified version of a Bayesian model of generalization from multiple examples that was proposed by Shepard and show similarities to human colour categorization. (+info)
Stability of functional equivalence and stimulus equivalence: effects of baseline reversals.
(7/150)
Functional equivalence and stimulus equivalence classes were established, reversed, and tested for stability with college students. Functional stimulus classes were established using a task in which students were trained to say nonsense words in the presence of arbitrarily assigned sets of symbols. Computer-controlled speech-recognition technology was used to record and analyze students' vocal responses for accuracy. After the establishment of stimulus classes was demonstrated with a transfer-of-function test, the effects of reversing selected baseline simple discriminations were assessed during an additional transfer-of-function test and a follow-up test that occurred several weeks later. With the same students, stimulus equivalence classes were established and demonstrated with computerized matching-to-sample procedures. The effects of reversing selected baseline conditional discriminations also were assessed during a postreversal equivalence test and a follow-up test. Both functional stimulus classes and stimulus equivalence were sensitive to contingency reversals, but the reversals with stimulus equivalence closses affected stimulus class organization whereas reversals with functional stimulus classes did not. Follow-up performances were largely consistent with the original baseline contingencies. The similarities and differences between stimulus equivalence and functional equivalence are related to the specific contingencies that select responding in the presence of the stimuli that form the classes. (+info)
Setting generality and stimulus control in autistic children.
(8/150)
This study was designed to assess the transfer of treatment gains of autistic children across settings. In the first phase, each of 10 autistic children learned a new behavior in a treatment room and transfer to a novel extra-therapy setting was assessed. Four of the 10 children showed no transfer to the novel setting. Therefore, in the second phase, each child who failed to transfer participated in an analysis of stimulus control in order to determine the variables influencing the deficit in transfer. Eachof the four children who did not transfer were selectively responding to an incidental stimulus during the original training in the treatment room. Utilizing a reversal design, each of the four children responded correctly in the extra-therapy setting when the stimulus that was functional during training was identified and introduced into the extra-therapy setting. The extreme selective responding and the resulting bizarre stimulus control found are discussed in relation to the issue of setting generality of treatment gains. (+info)