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PubMed1975

Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation.

Rabbits received 0 to 450 exposures of a tone conditioned stimulus (CS) prior to classical defensive conditioning of the nicitating membrane response based on an infraorbital eye shock unconditioned stimulus. Tone preexposure resulted in retarded conditioning in normal rabbits. This latent inhibition effect was not present in animals with bilateral dorsal hippocampectomy produced by aspiration. Control animals with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated animals. The failure of CS preexposure to retard conditioning in hippocampal rabbits was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the unconditioned response. A subsequent experiment employed combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitiory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. These findings were discussed in terms of Douglas' model of hippocampal function.

Acoustic Stimulation↗
PubMed1975

"Stimulus generalization" between differentiated visual, auditory, and central stimuli.

Cats were trained to discriminate between two different repetition rates of flicker and of click. Both approach-approach and avoidance-avoidance discriminations were used. After substantial overtraining, transfer of frequency discrimination was initiated to stimulation of the reticular formation using bursts of electrical pulses at the same two repetition rates. Significant levels of discriminated performance were obtained in all cats very quickly, indicating good cross-modal transfer between the peripheral discriminanda and the central stimuli. The literature on stimulus generalization and cross-modal transfer is reviewed and the findings of this experiment are discussed in that context. Certain conditions are defined which, if satisfied, justify the interpretation that stimulus generalization or rapid cross-modal transfer indicate that facilitation of subsequent tasks in a training sequence can be attributed to mediation by a specific neuronal mechanism established by training on a previous task. The present experiment was designed in view of such criteria. The evidence of good cross-modal transfer is interpreted to mean that brain mechanisms storing memories about discriminations between visual or auditory stimuli with different repetition rates can be effectively activated by gross electrical stimuli at the same repetition rates. Conflict trials were then carried out in which flicker or click at either frequency was contradicted by concurrent RF stimuli at the other frequency. As the current level of RF stimuli was parametrically increased, it was found that the central stimuli achieved almost complete control over the behavioral outcome in most cases. Concurrent transfer of training, using a counterbalanced training sequence, was then carried out to stimulation of the visual cortex, lateral geniculate, medial geniculate, and the intralaminar nuclei of the thalamus. In each case, rapid transfer was displayed by at least one animal. Once performance to brain stimulation at a given repition rate was established, little change was observed when the fine structure of the stimulus was altered by changing parameters of the stimulus burst. These findings are interpreted as providing support for a statistical theory of memory, since they constitute evidence that previously learned discriminative behavior can readily be elicited by compelling large ensembles of neurons in various brain regions to discharge with particular temporal patterns. It is difficult to reconcile these results with theories which postulate that learning establishes new synaptic pathways in which discharge must occur for memories to be retrieved.

Animals↗
PubMed1977

Subcutaneous injections of apomorphine, stimulus generalization and conditioning: serious pitfalls for the examiner using apomorphine as a tool.

This report shows that stimulus generalization occurs in rats conditioned by a single injection of apomorphine. The data suggest that apomorphine initially acts as an unconditioned stimulus (UCS) of an unconditioned response (UCR) that, in turn, produces stimuli which become conditioned stimuli (CS) of a conditioned response (CR) having a nature identical to that of the UCR. The study also shows that behaviour elicited by a subcutaneous injection of apomorphine depends on the part of the body selected for administration. The mentioned properties should be taken into account when apomorphine is used as a tool in studies on brain and behaviour.

Animals↗
PubMed1989

A role for stimulus generalization in conditional discrimination learning.

In each of three experiments on discrimination learning by rats, whether or not a 10-sec target stimulus was followed by food was determined by the nature of a 2-min background stimulus that accompanied it. A conditional discrimination was employed in Experiment 1 such that background A indicated food would follow one target but not the other, whereas this relationship between the targets and food was reversed in the presence of background B. Experiment 2 employed two feature-positive discriminations. Subsequent test trials revealed that the background for one discrimination was able to enhance responding during the target for the other discrimination. Experiment 3 employed a feature-positive and a feature-negative discrimination prior to test trials in which each target was presented separately during a compound of both background stimuli. The compound enhanced responding to the target from the feature-positive discrimination and reduced it to the target from the feature-negative discrimination. We suggest that to accommodate all these findings, the best explanation is provided by a configural model of Pavlovian conditioning.

Animals↗
PubMed1978

The central tendency effect in stimulus generalization: the effect of sex of subject.

Eighty male and 80 female college students were shown a stimulus light of 525 nm, following instructions to remember it, and then were immediately tested for generalization (recognition) with a successively presented set of stimuli including 525 nm and six longer wavelength values. Subjects rated each test stimulus on a 6-point scale ranging from "surely same" as the original stimulus to "surely different." Both men and women showed a central tendency shift. Although the stimulus perceived as most likely to be the original (the mode) shifted to 545 nm in both groups, the men showed a greater mean shift than the women. Shifting was nearly complete in both groups within the first series of test stimuli with the men shifting faster. These findings replicate a 1972 report by Giurintano of greater central tendency shift in men than in women in a line angle generalization task, challenging an assumed analogy between our generalization task and the rod-and-frame test, in which women typically show the greater distortion. The analysis of central tendency shift within the first test series reveals that it occurs much earlier than previously believed.

Discrimination, Psychological↗
PubMed1988

Limited stimulus generalization between delta 9-THC and diazepam in pigeons and gerbils.

Pigeons trained to discriminate between the presence and absence of delta 9-THC (0.56 mg/kg, IM, intramuscularly) were tested with diazepam (5.6-30 mg/kg), administered IG (intragastrically), and were found to generalize the response associated with the THC training to the diazepam treatment only to a limited extent. Two groups of gerbils trained to discriminate between the presence and absence of IP (intraperitoneally) injected benzodiazepine agonists (5.6 mg/kg of diazepam and Ro 11-3128, respectively) generally did not generalize the drug response to IP administered THC (5.6 and 17.5 mg/kg). In addition, substitution testing with the dopamine autoreceptor blocker (+)-3PPP yielded non-drug responding in the pigeons. Hence neither proposed structural similarity between 3-PPP and THC, nor purported anxiolytic activity by 3-PPP (see Introduction) matched the THC-induced stimulus effects. The data are discussed with reference to the specificity of the THC cue or stimulus.

Animals↗
PubMed1975

Stimulus generalization of suppression in rats following aversively motivated instrumental or Pavlovian training.

Following 100 or 300 avoidance training trials, instrumental subjects and their yoked Pavlovian counterparts were tested for generalization of lick suppression along the frequency dimension of the avoidance conditioned stimulus. Gradients of stimulus control were evident after 300 instrumental avoidance training trials, and additional intradimensional Pavlovian discrimination training further sharpened the gradients. After 100 trials, the yoked Pavlovian subjects suppressed more than their instrumental counterparts. However, with increased Pavlovian training, flatter gradients with decreased suppression were obtained. Results from a second experiment revealed that, whereas Pavlovian experience decreased suppression to the tone, subjects suppressed drinking in the presence of static, environmental cues. Data from both experiments supported interpretations that stress the role of response control over environmental events.

Acoustic Stimulation↗
PubMed1989

Evidence for perceptual masking of the discriminative morphine stimulus.

Morphine-amphetamine and morphine-naltrexone interactions were examined in three groups of White Carneaux pigeons (n = 3), which were trained in a two-choice drug discrimination procedure under a FR-30 schedule of food reinforcement using 3.2 mg/kg morphine and saline as discriminative stimuli. Once stimulus control was acquired by these initial training stimuli, the training doses of morphine were gradually changed to 1.0 mg/kg for group A and to 10 mg/kg for group C. The three groups differed in the minimum dose required for stimulus control and the drugs to which the training stimulus generalized. Stimulus generalization to amphetamine was inversely related to training dose. Amphetamine potentiated the discriminative stimulus properties of morphine. Naltrexone blocked the discriminative stimulus properties of morphine to varying degrees, which appeared to be limited by the training dose and the rate-suppressing effects of naltrexone when administered alone. Challenging the morphine stimulus with amphetamine resulted in a qualitatively similar blockade. This blockade was a direct function of the morphine training dose. It is argued that MS-AMP interactions result in perceptual masking of the MS stimulus, which can be differentiated from pharmacological antagonism by NTX. Two other challenge drugs, ketamine and sodium pentobarbital, did not alter stimulus control by morphine.

Animals↗
PubMed1989

Time-dependent generalization of morphine stimulus properties to meperidine: antagonism by naloxone.

The time course of the stimulus generalization to morphine by meperidine (20 mg/kg) was determined in rats trained to discriminate morphine (10 mg/kg) from saline in a standard two-lever procedure with food reinforcement. It was found that morphine lever selection following meperidine was a strictly time-dependent phenomenon. Naloxone (0.3 mg/kg) antagonized the stimulus properties of both morphine and meperidine; however, the antagonism was significantly more pronounced against morphine. The results suggest that there may be certain differences in the neuropharmacology of the stimulus properties of morphine and meperidine.

Animals↗
PubMed1985

Mechanistic studies on DOM as a discriminative stimulus.

Ten rats were trained to discriminate racemic DOM (1.0 mg/kg, IP) from saline using a standard two-lever operant procedure. Once responding was stable, these animals were administered doses of lisuride and the purported 5-HT1 agonist 8-OH DPAT in tests of stimulus generalization. DOM-stimulus generalization occurred with lisuride, but not with 8-OH DPAT. These animals were also administered doses of LY-53,857, ritanserin, CP-52,215, and THT in tests of stimulus antagonism. Each of these agents possesses a significant affinity for 5-HT2 binding sites, and each effectively attenuated the DOM-stimulus. These results, coupled with our earlier findings, support the hypothesis that DOM may be producing its stimulus effects via a 5-HT2-related mechanism.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

Mechanistic investigation of the stimulus properties of 1-(3-trifluoromethylphenyl)piperazine.

Using a standard two-lever operant procedure with rats trained to discriminate 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (0.5 mg/kg) from saline, tests of stimulus antagonism and stimulus generalization were performed to better understand the stimulus properties of this agent. The agents examined for ability to antagonize the TFMPP stimulus were prazosin, quipazine, zacopride, buspirone, 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), 1-(2-methoxyphenol)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190), haloperidol, and 1-(2-pyrimidinyl)piperazine (1-PP); only buspirone attenuated the response to TF-MPP. In separate experiments, the lowest nondisrupting dose of buspirone (1.2 mg/kg) caused a rightward shift of the TFMPP dose-response curve (TFMPP alone, ED50 = 0.19 mg/kg; TFMPP + buspirone, ED50 = 0.43 mg/kg). In addition, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93, 129), 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)pyrolo[1,2-a]quinox ali ne (CGS 12066B), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 3-chlorophenylbiguanide (mCPBG), NAN-190, nisoxetine, zacopride, 1-PP, (+)-N-allylnormetazocine ((+)-NANM), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) were analyzed in tests of stimulus generalization. The TFMPP stimulus generalized only to CGS 12066B (ED50 = 4.2 mg/kg) and (+)-NANM (ED50 = 8.8 mg/kg). Tests with DOI and MDMA resulted in partial generalization. Up to doses that disrupted behavior, all other agents had little effect on TFMPP-appropriate responding. The results of these and other published studies suggest roles for 5-hydroxytryptamine 1B (5-HT1B), 5-HT1C, and, possibly, sigma-receptors in the mediation of the TFMPP stimulus and indicate a lack of involvement of 5-HT1A, 5-HT2, dopaminergic, and adrenergic mechanisms in this behavior.

Animals↗
PubMed1991

The discriminative stimulus effects of diazepam in rats at two training doses.

Two groups of rats were trained to discriminate either a low (1 mg/kg) or a high (10 mg/kg) intraperitoneal dose of diazepam from vehicle injections in a two-lever, food-reinforcement procedure. Comparison of the dose-response curves demonstrated a difference in the intensity of the stimulus effects. A number of benzodiazepine agonists and partial agonists were tested for stimulus generalization. The stimulus effect in both groups of rats generalized fully to triazolam, alprazolam, adinazolam and pentobarbital. Ro 17-1812 occasioned nearly full generalization in both groups of rats with a shallow dose-response slope. The low-, but not the high-dose stimulus effect generalized to the following compounds: CL 218872, ZK 91296 (ethyl-5-benzyloxy-4-methoxymethyl-B-carboline-3-carboxylate), CGS 20625 (2-(4-methoxyphenyl)-2,3,5,6,7,8,9,10-octahydrocyclohepta(b)pyrazo lo(3,4- d)pyridin-3-one) and U-78875 (3-(5-cyclo-propyl-1,2,4-oxadiazol-3-yl)-5-(1- methylethyl)imidazol(1,5-a)quinoxalin-4(5H)-o-ne). Flumazenil, FD-7142 (N-methyl-beta-carboline-3-carboxamide), buspirone and morphine occasioned predominantly vehicle-appropriate responses in both groups of rats. In the low-dose group, pretreatment with flumazenil (10 mg/kg) reduced responding on the diazepam-lever for the following compounds: diazepam, Ro 17-1812 (cyclopropylmethyl-(S)-8-chloro-12,12a-dihydro- 9-oxo-9H,11H-aceto(2,1-C)imidazo(1,5-a)(1,4)benzo-diazepine-1-carboxylat e), ZK 91296, CGS 20625, CL 218872 and U-78875.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprazolam↗
PubMed1986

Discriminative stimulus properties of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT).

Using a two-lever operant procedure, eleven rats were trained to discriminate 0.2 mg/kg of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) from saline using a variable-interval 15 sec schedule of reinforcement. Once trained, these animals were used in a series of stimulus generalization and stimulus antagonism studies. The 8-OH DPAT-stimulus did not generalize to the 5-HT1B agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) or the 5-HT2 agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), nor could it be attenuated by pre-treatment of the animals with the 5-HT2 antagonist ketanserin. Low doses of spiperone and propranolol were without effect on 8-OH DPAT-appropriate responding, whereas higher doses of these agents resulted in disruption of behavior. Some preliminary structure-activity data were also obtained using several related tetralin analogs. The results of this study demonstrate that the serotonin agonist 8-OH DPAT serves as a discriminative stimulus in rats and that it produces stimulus effects that are probably not 5-HT1B or 5-HT2-mediated.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1991

Inverse agonist properties of the THBC discriminative stimulus: asymmetrical generalization with FG 7142.

Male rats were trained to discriminate the stimulus properties of the beta-carbolines 1,2,3,4-tetrahydro-beta-carboline (THBC) (15.0 mg/kg) or FG 7142 (5.0 mg/kg) from vehicle in a two-lever, food-motivated operant task. Consistent with the serotonergic properties of THBC, administration of the 5HT1B agonists TFMPP and mCPP to THBC-trained rats resulted in THBC-appropriate responding. Norharmane, a beta-carboline metabolite of THBC, also mimicked the THBC discriminative stimulus. In contrast, the benzodiazepine receptor partial inverse agonist FG 7142, the anxiogenic/convulsant pentylenetetrazole (PTZ), two physiological stressors and the alpha 2 adrenergic antagonists yohimbine and idazoxan failed to produce THBC-appropriate responding. In the FG 7142-trained rats, THBC and norharmane dose-dependently mimicked the FG 7142 discriminative stimulus. This generalization was not based upon the serotonergic properties of THBC and norharmane since administration of the serotonin agonist mCPP to FG 7142-trained rats failed to produce FG 7142-appropriate responding. The ability of THBC to substitute for the FG 7142 discriminative stimulus was antagonized by the benzodiazepine receptor mixed agonist/antagonist CGS 9896 and the benzodiazepine receptor antagonist RO 15-1788, indicating that THBC produces an inverse agonist stimulus in FG 7142-trained rats. These results suggest that THBC produces a discriminative stimulus which consists of both serotonergic and inverse agonist components.

Animals↗
PubMed1988

Site-selective serotonin agonists as discriminative stimuli.

Various direct- and indirect-acting serotonin (5-HT) agonists serve as training drugs in tests of stimulus control of behavior; such agents include: 5-hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine, and fenfluramine. However, with the recent discovery of multiple populations of central 5-HT binding sites, the concept of site-selective serotonergic agents needs to be addressed. Certain 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropanes such as DOM (4-methyl), DOB (4-bromo), and DOI (4-iodo) appear to be 5-HT2-selective agonists and serve as effective training drugs in rats. Stimulus generalization occurs among these agents regardless of which is used as the training drug, although stimulus generalization does not occur with 5-HT1A-selective agonists [e.g., 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT)] or with 5-HT1B-selective agonists [e.g., 1-(3-trifluoromethylphenyl)piperazine (TFMPP)]. 8-OH DPAT and TFMPP also serve as training drugs; the 8-OH DPAT-stimulus generalizes to other 5-HT1A agonists, but not to 5-HT1B or 5-HT2 agonists, whereas the TFMPP-stimulus generalizes to other 5-HT1B agonists, but not to 5-HT1A or 5-HT2 agonists. Classical serotonin antagonists, most of which are rather selective for 5-HT2 sites, and 5-HT2-selective antagonists are able to block the stimulus effects of DOM, DOB, and DOI, but not those of 8-OH DPAT or TFMPP. The results of such studies reveal that, in rats, site-selective 5-HT agonists produce stimulus effects that are also selective; although generalization may occur with nonselective 5-HT agonists, animals trained to discriminate site-selective 5-HT agonists apparently do not recognize other 5-HT agonists that are selective for a different site. Animals trained to discriminate such agents from saline might be useful for the identification and/or investigation of novel site-selective agonists and antagonists (for example, the 8-OH DPAT-stimulus generalizes to members of a new class of anxiolytics that display high affinity for 5-HT1A binding sites), and might also aid in the overall understanding of central serotonergic mechanisms.

Animals↗
PubMed1989

A developmental study of filtering in visual attention.

Children aged 4, 5, and 7 years and adults aged 20 years performed a speeded classification task designed to isolate several sources of interference in visual selective attention. On each trial, observers responded to 1 of 4 targets which were mapped to 2 responses. On some trials the targets were also flanked by distractor stimuli, which observers were asked to ignore. The interference measures examined the effects of attentional set, increases in feature number, increases in feature type, response competition, and stimulus generalization. All but 1 of the measures (stimulus generalization) produced reliable interference in the adult observers. However, only 2 of the measures (attentional set, increases in feature number) produced reliable interference in children. The implications of these findings for theories of attentional development are discussed.

Adult↗
PubMed1988

Chlorphentermine may produce dual stimulus effects: a preliminary investigation.

1. Rats were trained to discriminate injections of either (+)-amphetamine (0.75 mg/kg) or (+/-)-fenfluramine (1.5 mg/kg) from saline in a two-lever drug discrimination task. 2. After stable discrimination performances were attained in each group, stimulus generalization studies were conducted with amphetamine, fenfluramine, and chlorphentermine. 3. Stimulus generalization (substitution) did not occur between amphetamine and fenfluramine when either drug was used as the training stimulus. 4. In contrast, both the amphetamine stimulus and the fenfluramine stimulus generalized completely to chlorphentermine. 5. Taken together, the results suggest that chlorphentermine may be capable of producing dual stimulus effects in animals.

Animals↗