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PubMed1998

Separation of the locomotor stimulant and discriminative stimulus effects of cocaine by its C-2 phenyl ester analog, RTI-15.

During a routine evaluation of several analogs of cocaine, we observed that the C-2 phenyl ester, RTI-15, appeared to suppress motor activity in rats. We subsequently examined RTI-15 for its cocaine-like stimulus effects as well as for its locomotor activity effects. RTI-15 dose-dependently generalized from the cocaine stimulus in rats trained to discriminate 10 mg/kg cocaine from saline with complete substitution (> or = 80% cocaine-lever responding) occurring at 24 mg/kg. During automated locomotor activity tests in mice, cocaine (3-60 mg/kg) dose-dependently increased activity counts and movement time across the entire 1 h test session. RTI-15, however, had little affect on activity counts and movement time from 10-30 mg/kg, and decreased these measures at 60 mg/kg, the highest dose tested. These results indicate that while changing the C-2 methyl ester of cocaine to a C-2 phenyl ester increases dopamine-transporter selectivity, it dissociates its locomotor activity effects from its discriminative stimulus effects suggesting that the underlying mechanisms mediating these effects are not identical.

Animals↗
PubMed1982

Discriminative stimuli produced by clonidine: an investigation of the possible relationship to adrenoceptor stimulation and hypotension.

In a leverpressing operant procedure, male rats were trained to respond for food reinforcement on one lever after an injection of clonidine (0.04 mg/kg) and to respond on an alternate lever for food reinforcement after an injection of saline. All 36 rats learned to discriminate the drug reliably from saline, thereby indicating that clonidine produces discriminative interoceptive stimuli. The discriminative stimulus was both dose- and time-dependent, with an ED50 of 0.018 mg/kg and an optimum time of action occurring from 15 to 60 min after injection. Although clonidine produced a reduction in response rate, this was not the basis of the discriminative stimulus as other drugs with similar depressant action did not generalize. The clonidine stimulus was dose-dependently antagonized by the alpha-2 adrenergic antagonist, yohimbine, whereas receptor antagonists of alpha-1 adrenergic, beta adrenergic, dopaminergic, serotonergic, cholinergic or opioid systems were ineffective in blocking the interoceptive stimulus produced by clonidine Lofexidine, guanabenz and methyldopa, all centrally acting hypotensive drugs that act through alpha-2 adrenoceptor mechanisms dose-dependently generalized to the clonidine cue, whereas hydralazine, minoxidil, propranolol and prazosin, hypotensive drugs acting through other mechanisms, did not generalize. These results suggest that clonidine produces interoceptive stimuli that are discriminable by rats and mediated through central alpha-2 adrenoceptor stimulation.

Animals↗
PubMed2004

How learning one category influences the learning of another: intercategory generalization based on analogy and specific stimulus information.

We investigated the effect of learning one category structure on the learning of a related category structure. Photograph-name combinations, called identifiers, were associated with values of four demographic attributes. Two problems were related by analogous demographic attributes, common identifiers, or both to examine the impact of common identifier, related general characteristics, and the interaction of the two variables in mediating learning transfer from one category structure to another. Problems sharing the same identifier information prompted greater positive transfer than those not sharing the same identifier information. In contrast, analogous defining characteristics in the two problems did not facilitate transfer. We computed correlations between responses to first-problem stimuli and responses to analogous second-problem stimuli for each participant. The analogous characteristics produced a tendency to respond in the same way to corresponding stimuli in the two problems. The results support an alignment between category structures related by analogous defining characteristics, which is facilitated by specific identifier information shared by two category structures.

Generalization, Psychological↗
PubMed1975

Effects of stimulus similarity in discrimination training upon wavelength generalization in pigeons.

Thirty pigeons were given variable interval training to peck a 555-nm. light and then were tested for wavelength generalization. The subjects were later assigned to 1 of 3 groups, matched for both relative generalization slope and response rate. One group then received successive discrimination training between the 555-nm. stimulus (S+) and a vertical white line on a 555-nm. background (S minus); another group experienced the same S+ but a vertical white line on a black background as S minus. A third group received a comparable amount of single stimulus training with the 555-nm. value. On a second wavelength generalization test, the first group yielded greater sharpening of generalization than the second group, whereas the third group showed no change from Test 1. These results indicate that the sharpening of generalization gradients by discrimination training is directly related to the similarity of the discrimination training stimuli.

Animals↗
PubMedDate not supplied

[Postsynaptic mechanism of habituation of turtle cortical neurons to moving stimuli].

An investigation was made into the change in the amplitude of evoked potentials and intracellular slow potentials of the turtle general cortex units in response to a periodic movement of a monotonous stimulus, a black band, across the visual field. The recorded depression of responses possesses all the properties of habituation. The first presentations of the monotonous stimulus produce a generalized habituation, gradually replaced by a selective habituation to the monotonous stimulus, as the number of stimulations increases. It has been shown that it is possible to disinhibit the amplitudes of the evoked potentials and intracellular slow potentials of cortical neurones to moving black bands which form part of the monotonous stimulus. A conclusion has been drawn that habituation of the turtle cortical units to moving stimuli is due to a postsynaptic mechanism.

Animals↗
PubMed1994

Textual prompts as an antecedent cue self-management strategy for persons with mild disabilities.

Providing learners written task analyses to be used as textual prompts was examined as a self-management strategy for persons with mild disabilities. Initially, modeling, corrective verbal feedback, and contingent descriptive praise were employed to train participants to use the written task analysis to perform one home maintenance task. Subsequently, participants were tested on their use of different task analyses combined with general feedback to perform two novel home maintenance tasks. No training was provided on how to use these new task analyses. Either a multiple baseline or a multiple probe across settings experimental design was used to control extraneous variables. Results indicated that the written task analyses served as self-administered textual prompts and, along with general feedback, provided stimulus control for the second and third tasks. When the self-management task analyses and general feedback were withdrawn, transfer of stimulus control occurred to the natural discriminative stimuli for the majority of tasks. The research suggests that written task analyses, as presented in the present study, may have utility for the self-management of instruction by persons with mild disabilities.

Adult↗
PubMed2006

Effects of S+ and S- separation on gradient shifts in humans.

Following single stimulus training, responding during a generalization test tends to be distributed around the positive stimulus (S+). However, if participants are trained instead to discriminate the S+ from a negative stimulus (S-), the response gradient often shifts away from the S- and toward the opposite end of the stimulus continuum. In this experiment, the author examined the basis of gradient shifts with 72 college undergraduates. The research especially examined how gradient shifts are affected by the physical similarity of the S+ and the S- and by the ease with which the two stimuli can be compared. For the former manipulation, the author randomly assigned participants to either a control condition in which only the S+ was shown or a discrimination condition in which the S- was either near to or far from the S+ on the continuum. For the latter manipulation, the author randomly assigned participants to a condition in which S+ and S- presentations were separated by intervals of 1, 15, or 30 s. The results showed that marked shifts occurred when the S+ and S- were relatively similar, but temporal separations did not affect responding.

Discrimination Learning↗
PubMed1992

Discriminative stimulus effects of alprazolam and diazepam: generalization to benzodiazepines, antidepressants and buspirone.

Rats in one group were trained to discriminate alprazolam (1.0mg/kg, i.p.) and in another group diazepam (3.0mg/kg, i.p.) from saline in a two-lever drug discrimination procedure. Food presentation occurred after 10 consecutive responses on the lever associated either with the training drug or with saline. Alprazolam, diazepam, lorazepam and chlor diazepoxide increased responding on the drug-associated lever in a comparable dose-related manner in both groups of rats: the relative order of potency was lorazepam >/= alprazolam > diazepam >/= chlordiazepoxide. Flumazenil (10.0mg/kg, i.p.) attenuated the effects of the training drugs. A range of doses of buspirone and four drugs having antidepressant properties (amitriptyline, fluoxetine, cericlamine, imipramine) then were studied in both groups of rats. All five drugs caused approximately 40% increases (group mean) in drug-appropriate responding in alprazolam-trained rats whereas only amitriptyline partially substituted for diazepam. The results indicate that alprazolam has interoceptive stimulus effects that overlap with the stimulus effects of diazepam, yet the effects of alprazolam may not be identical to those of diazepam because the antidepressant drugs and buspirone substituted partially for alprazolam but generally not for diazepam.

Journal Article↗
PubMed1984

Regulation of gonadotropin secretion during lactation.

Lactation in the rat is characterized by an inhibition of ovarian cyclicity which correlates with a suppression of basal gonadotropin secretion, a decrease in the magnitude of estrogen-induced LH surges and a decrease in the postcastration rise en LH and FSH. Furthermore, pulsatile administration of GnRH (0.4 ng GnRH every 50 min) fails to elicit LH pulses in females nursing 8 pups but produces normal basal LH pulses in females nursing 2 pups. There is a good correlation during lactation among pituitary GnRH receptor content, pituitary responsiveness to GnRH and basal LH secretion. All of these parameters are greatly decreased in the presence of an 8-pup suckling stimulus but are generally normal in the presence of a 2-pup suckling stimulus. Taken together with data from other laboratories suggesting that GnRH positively regulates its own receptors, these data suggest that a large suckling stimulus decreases GnRH release from the hypothalamus. This hypothesis is supported by studies in which GnRH release in lactating rats was indirectly assessed by examining the pulsatile pattern of LH secretion. In intact rats suckling 2 or 8 pups on day 10 postpartum, the pattern of LH secretion was uniformly nonpulsatile. The suppression of pulsatile GnRH release in intact females suckling 2 pups does not appear to be due to the small suckling stimulus itself, because ovariectomized females suckling 2 pups exhibited pulsatile LH secretion on day 10 postpartum, but may be due to some ovarian factor acting within the CNS to inhibit GnRH release. In contrast, in ovariectomized females suckling 8 pups, pulsatile LH secretion was completely suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Teachers' generalized use of delay as a stimulus control procedure to increase language use in handicapped children.

In Experiment 1, classroom teachers were taught to delay their offers of help in naturally occurring situations, and thereby to provide additional opportunities for language use by six moderately retarded language-delayed children. The teachers introduced this delay technique in a multiple-baseline design across the six children. As delays were used, child verbal initiations increased. Follow-up assessment showed that teachers were maintaining greater than baseline levels of the delay technique after 10 weeks. Experiment 2 replicated the findings of Experiment 1, and included a more thorough maintenance assessment, while focusing on teachers' generalization of the delay technique. Teachers were found to generalize their use of delay to 56% of their monitored untaught opportunities. The two experiments show that (a) the delay technique is quick to teach and simple to implement, (b) delays do provide opportunities for children to initiate, (c) teachers can generalize their use of delay to novel self-selected situations, and (d) teachers can maintain their use of delays over time.

Behavior Therapy↗
PubMed2006

Generalization of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists U-50,488H, but not TRK-820 in rats.

Generalizations of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists in rats were examined. Phencyclidine, MK-801, and ketamine, non-competitive NMDA-receptor antagonists, generalized to the discriminative stimulus effects of U-50,488H, but not those of TRK-820, whereas (+/-)-3-(2-carbaxypiperazine-4-yl) propyl-1-phosphonic acid (CPP), a competitive NMDA-receptor antagonist, and ifenprodil, an NR1/NR2B NMDA-receptor antagonist, did not, suggesting that non-competitive NMDA-receptor antagonists possess U-50,488H-like discriminative stimulus effects in rats. Since U-50,488H and phencyclidine both induce aversive effects, our findings indicate that the cue of the discriminative stimulus effects of U-50,488H and non-competitive NMDA-receptor antagonists may be associated with their aversive effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Development of distortion product emissions in the gerbil: "filter" response and signal delay.

Amplitude and phase responses of distortion product otoacoustic emissions as a function of stimulus frequency ratio were measured for frequencies between 2 and 48 kHz, in Mongolian gerbils (Meriones unguiculates) aged 15 to 30 days after birth. After baseline measurements, furosemide was administered to distinguish active from passive emissions. At all ages, structure in the form of multiple peaks was observed in the amplitude responses of specific odd-order emissions. This structure depended on the emission frequency, not the stimulus frequency ratio, and did not generally depend on the stimulus amplitude. Nor was it dependent on the functioning of the cochlear amplifier: At moderate stimulus levels, the observed emission distribution simply shifted to lower amplitudes when the cochlear amplifier was made temporarily dysfunctional by furosemide injection. The center frequencies and widths of the peaks in the amplitude response did not generally change with age, except that the relative amplitudes of the higher-frequency peaks were increased in younger animals. At 2 kHz, however, the distribution showed other evidence of maturation, with the frequency of maximum emission moving downward with age. The phase responses yielded estimates of the round trip signal (group or traveling wave) delay. At a given frequency, the active signal delay typically decreased substantially with increasing stimulus level. However, there was a rapid variation in delay as the stimulus level passed the normal active-passive crossover level. At stimulus levels measured relative to the active-passive crossover level, i.e., either 20 or 30 dB lower, the active signal delay decreased only slightly with age. Overall, both filter response and signal delay characteristics were found to be essentially mature near the onset of hearing.

Acoustic Stimulation↗
PubMed1995

Discriminative stimulus properties of dextromethorphan in rats.

Male Sprague-Dawley rats were trained to discriminate dextromethorphan (DM, 30 mg/kg, ip) from saline using a standard two-lever, fixed ratio 10, food reinforcement procedure. The DM-saline discrimination was acquired, and a range of doses of DM produced a dose-related generalization to the DM-lever choice. Stimulus generalization tests were conducted with dextrorphan, an active metabolite of DM, and with drugs selected from different pharmacological families. Dextrorphan induced a full generalization to DM, but only at a dose higher than the DM training dose. Morphine, a mu opiate receptors agonist, and U 50488, a kappa opiate receptors agonist, failed to substitute for DM. Cyclazocine, a benzomorphan derivative, with high affinity for sigma receptors, was able to produce a complete generalization to DM, without a change in the number of rats responding. Dizocilpine (MK 801), a phencyclidine-like drug, produced a complete generalization, but only at a dose that markedly reduced the number of rats responding. Carbetapentane and caramiphen, antitussive drugs with high affinity for the 'specific DM receptors', failed to substitute for DM. These results show that the discriminative stimulus of DM, did not result primarily from its metabolism to dextrorphan; and the discriminative stimulus properties of DM appear to more closely resemble those of cyclazocine than those of the other drugs tested. This suggests a role of sigma receptors in the mediation of the DM stimulus. These experimental data are discussed with reference to the cyclazocine-like subjective effects produced in man by large doses of DM.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Generalization among related complex odorant mixtures and their components: analysis of olfactory perception in the spiny lobster.

We investigated the processing of odorant mixtures containing two to seven components by the spiny lobster Panulirus argus. The chemicals tested were food-related compounds that are attractive to spiny lobsters, and include adenosine-5'-monophosphate, betaine, L-cysteine, L-glutamate, DL-succinate, taurine, and ammonium. Components were tested at concentrations that produced search behavioral responses of equal magnitude in unconditioned animals. Responses of unconditioned animals to mixtures and their components reveal hypoadditivity, in which the response to a mixture is less than the sum of the responses to that mixture's components. Aversive conditioning coupled with generalization testing was used to evaluate generalization and hence perceptual similarity between related mixtures. Animals were conditioned to either an individual odorant, a four-compound mixture, or a seven-compound mixture, followed by generalization testing with submixtures or larger mixtures containing the conditioned stimulus. Animals tended not to generalize, but significant generalization between a more simple conditioned stimulus and more complex mixtures containing that conditioned stimulus occurred in 2 of 11 cases, and significant generalization between a conditioned mixture and its submixtures was observed in 4 of 9 cases. Both the number and chemical identity of components of mixtures may contribute to the degree of generalization between mixtures. Overshadowing, in which the ability to learn about a chemical is affected by simultaneous presentation of other chemicals, occurred in two of three cases. We discuss implications of these findings with respect to elemental and configural processing of odorant mixtures in the spiny lobster, possible neural mechanisms responsible for these results, and the potential utility of generalization and overshadowing to the spiny lobster's natural behavior.

Animals↗
PubMed1998

Attempts to classify dependence-liable drugs by using a simple drug-discrimination test in mice.

1. In a simple discrimination test using a two-compartment shuttle box with mice, we examined the action properties of dependence-liable drugs. In mice trained to discriminate morphine from saline, neither methamphetamine (MAP) nor cocaine (COCA) was generalized to the discriminative stimulus effects of morphine. 2. Similarly, in mice trained to discriminate MAP from saline, COCA, which is known to have neuronal mechanisms in common with MAP, was generalized to the stimulus effects of MAP, but morphine was not. 3. Dihydroetorphine (DHE), which has receptor mechanisms in common with morphine, was generalized to the discriminative stimulus effects of morphine, whereas it was not generalized to the effects of MAP. Thus, the present discrimination test might be useful for the first screening of compounds with unknown neuronal mechanisms, particularly for classification into groups having separate neuropharmacological mechanisms in common.

Analgesics, Opioid↗
PubMed2002

Stimulus-based lexical distinctiveness as a general word-recognition mechanism.

Word recognition is generally assumed to be achieved via competition in the mental lexicon between phonetically similar word forms. However, this process has so far been examined only in the context of auditory phonetic similarity. In the present study, we investigated whether the influence of word-form similarity on word recognition holds in the visual modality and with the patterns of visual phonetic similarity. Deaf and hearing participants identified isolated spoken words presented visually on a video monitor. On the basis of computational modeling of the lexicon from visual confusion matrices of visual speech syllables, words were chosen to vary in visual phonetic distinctiveness, ranging from visually unambiguous (lexical equivalence class [LEC] size of 1) to highly confusable (LEC size greater than 10). Identification accuracy was found to be highly related to the word LEC size and frequency of occurrence in English. Deaf and hearing participants did not differ in their sensitivity to word LEC size and frequency. The results indicate that visual spoken word recognition shows strong similarities with its auditory counterpart in that the same dependencies on lexical similarity and word frequency are found to influence visual speech recognition accuracy. In particular, the results suggest that stimulus-based lexical distinctiveness is a valid construct to describe the underlying machinery of both visual and auditory spoken word recognition.

Adult↗
PubMed1989

Mu-opioid component of the ethylketocyclazocine (EKC) discriminative stimulus in the rat.

The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the EKC cue at doses of 0.3 and 10 mg/kg, respectively. The putative mu-opioid receptor agonists morphine (M) and fentanyl also dose-dependently generalized with the EKC stimulus. The generalization of M with EKC was not symmetrical, EKC and U50,488H produced little or no M-appropriate responding in rats trained to discriminate 3.0 mg/kg M (SC) from saline. This generalization pattern may reflect a lack of opioid receptor selectivity of the EKC stimulus. However, distinct mu-opioid and kappa-opioid components of the EKC cue could be identified using graded doses of naloxone in EKC-trained rats. The discriminative effects of morphine and fentanyl were blocked completely by doses of 0.1-1.0 mg/kg naloxone, whereas doses of naloxone 3-10 times greater were necessary to block the discriminative effects of EKC and U50,488H. These results suggest that EKC produces a complex discriminative stimulus with mu-opioid and kappa-opioid components that can be separated using antagonists such as naloxone.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Endogenous adenosine-receptive systems do not mediate the discriminative stimulus properties of ethanol.

Adenosine is an endogenous neuromodulator with depressant effects on CNS neurons. Adenosine agonists produce biphasic effects on activity, decreases in operant response rate, and anticonvulsant effects. These effects are similar to some of the behavioral effects of ethanol. In addition, it has recently been shown that relative sensitivities to some of the behavioral effects of ethanol and purinergic drugs are similar in inbred strains of mice. These findings have prompted the speculation that ethanol's behavioral effects may be mediated by an agonist action on adenosine-receptive neurons. The present study provided a direct test of this hypothesis with respect to the discriminative stimulus properties of ethanol. In this study, neither the A1 receptor agonist N6-cyclohexyladenosine nor the A2 receptor agonist N6-ethylcarboxamide adenosine produced significant generalization to the ethanol stimulus. In addition, neither the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine nor the adenosine uptake inhibitor dipyridamole were able to enhance the level of ethanol-appropriate responding seen after a low dose of ethanol. Both caffeine and 8-phenyltheophylline partially but significantly antagonized the stimulus properties of ethanol. However, the doses required to achieve these effects were much higher than those needed to block adenosine receptors. These findings strongly suggest that the discriminative stimulus properties of ethanol are not mediated through an agonist action on adenosine-receptive neurons.

Animals↗