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PubMed1989

Behavioral interaction between cocaine and caffeine: a drug discrimination analysis in rats.

The effects of caffeine upon the discriminative and rate-altering effects of cocaine were examined in rats. Using a food-reinforced two-lever operant procedure, 12 Sprague-Dawley male rats were trained to discriminate between 10 mg/kg cocaine and saline. Stimulus generalization tests with both cocaine and amphetamine resulted in a dose-related increase in cocaine-appropriate responding. A variable response rate topography was produced by cocaine. Caffeine also engendered a dose-related increase in cocaine-appropriate responding and resulted in a potency ratio of 15:1 when compared to cocaine. In contrast, increasing doses of caffeine produced a biphasic response rate function (first increases and then decreases). Response choice data suggested a potency relationship of amphetamine greater than cocaine greater than caffeine. Caffeine potentiated the discriminative stimulus properties of cocaine. Isobolographic analysis characterized this interaction as simple additivity. However, caffeine's effects upon the rate-altering effects of cocaine resulted in a biphasic interaction pattern. With low doses of cocaine in combination with various doses of caffeine, the interaction for rate reduction is best categorized as "supra-additive," in contrast, increasing either the cocaine dose or caffeine dose could change the interaction to simple additivity and/or infra-additivity.

Animals↗
PubMed2000

The design and application of three speaker-based stimulating devices for cutaneous stimulation in anesthetized and awake animals.

Those wishing to study neuronal plasticity in sensory systems are confronted by the need to deliver equivalent stimuli to the organism at time intervals separated by hours, days or months. This problem is particularly acute in the somatosensory system where delivering an equivalent stimulus generally requires a second physical contact with the same point on a geometrically complex surface. This requirement is difficult to fulfill. We have designed two stimulators that avoid or minimize the importance of this requirement by obviating the need for the stimulator to be at a fixed distance from the skin. As well, we have redesigned a system for whisker stimulation originally proposed by Simons. The first stimulator is appropriate for experiments in anesthetized animals; the surface to be stimulated is immersed in water warmed to body temperature and the tactile stimulus is generated as an hydraulic pulse. The second uses a high velocity pulse of air shaped so that it can be transmitted significant distances without attenuation. The redesign of the Simons' vibrissa stimulator provides larger amplitude displacements and lower controlling voltages more readily generated by equipment normally found in laboratories. We also described the design of a chamber for restricting the awake rat during chronic study and the electrodes used for recording and for delivery of drugs in awake animals held in such a chamber.

Air Pressure↗
PubMed2005

Short-term inter-visit variability of erg amplitudes in normal subjects and patients with retinitis pigmentosa.

PURPOSE: To evaluate the short-term test/retest variability in visually normal subjects and patients with retinitis pigmentosa (RP), and to assess the effect of stimulus intensity and baseline amplitude on electroretinogram (ERG) variability. METHODS: Eighteen patients with RP and nine visually normal subjects had a series of three unilateral ERGs, with an inter-visit interval of no less than 2 days and no more than 2 weeks. Responses to dark-adapted and both light-adapted single flash and 32 Hz flicker stimuli were recorded from a dilated eye over a range of stimulus intensities. B-wave amplitudes were compared to baseline amplitudes recorded at initial visit, and the resulting inter-visit percent difference was compared between stimulus intensities. Inter-visit variability was determined by one-way repeated measures analysis of variance using a 95% confidence interval to calculate threshold criteria for significant change. Analysis of variance followed by Bonferroni test for pairwise comparison was used to test for differences in inter-visit variability between two RP patient subgroups (higher versus lower baseline amplitudes) and visually normal subjects. The effect of stimulus intensity on amplitude reproducibility was also assessed. RESULTS: Threshold for significant increase or decrease in inter-visit ERG amplitudes at a 95% confidence level for patients with RP and visually normal subjects was often at or above 25% and not infrequently at or above 40% for certain stimuli and test conditions. While no statistical difference in inter-visit variability was demonstrated between visually normal subjects and patients with RP who were arbitrarily categorized as having relatively higher baseline amplitudes, there was a difference between each of these two groups and a smaller group of patients with RP categorized as having lower baseline amplitudes. Although the authors could not demonstrate that percent inter-visit differences varied with stimulus intensity in either controls or patients with RP, the 32 Hz flicker stimulus generally produced less amplitude variability than either dark- or light-adapted single flash stimuli in patients with RP. CONCLUSIONS: When using ERG amplitude for monitoring either the natural history of functional loss in retinal disease or as an outcome measure during a therapeutic trial, it becomes vital to define inter-visit variability of ERG amplitudes. These findings suggest that a percentage of patients with RP with appreciably lower baseline ERG amplitudes may manifest greater inter-visit ERG amplitude variability than patients with RP with higher baseline amplitudes or controls. Stimulus intensity had no clinically significant effect on inter-visit amplitude variability.

Adult↗
PubMed1991

Effects of peer-mediated instruction on the acquisition and generalization of written capitalization skills.

This study investigated the effects of a peer teaching procedure, combined with student letter-writing activities, on the acquisition and generalization of capitalization skills. Three students, aged 9 years, obtained instruction from peer partners that included (a) an introduction and review of capitalization rules, (b) feedback on each participant's previous capitalization work, and (c) guided and independent practice on sentences that required capitalization. All three students demonstrated acquisition of the capitalization rules after participating in the teaching sessions with one or two peer partners. In addition, there were increases in capitalization accuracy in participants' letters to peers who did not serve as teaching partners, thus demonstrating a measure of across-peer (stimulus) generalization. Mixed results were obtained on a response generalization task (sentence writing). Finally, sentencing-writing activities also showed that two of the peer partners substantially improved their use of capitalization skills as a result of teaching the target students.

Child↗
PubMed1991

[Evaluation of the discriminative stimulus effect of an enkephalin analog, EK-399, in the rat].

Four groups of rats were trained to discriminate between the no-drug conditions (saline, s.c.) and the effect of s.c. injection of the novel enkephalin analog Tyr-D-Met (O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399, 1 mg/kg), morphine (3 mg/kg), ethylketocyclazocine (EKC, 0.3 mg/kg) or N-allylnormetazocine (NANM, 3 mg/kg) in a two-lever choice, water reinforced procedure. All groups of animals acquired the ability to discriminate EK-399, morphine, EKC or NANM from saline. Naloxone (0.03-0.3 mg/kg, s.c.) completely antagonized the discriminative stimulus effects of EK-399, morphine and EKC, but not that of NANM. In stimulus generalization tests, morphine (10 mg/kg) and buprenorphine (0.03 mg/kg), mu-opioid receptor agonists, completely substituted for EK-399 in groups trained with EK-399, whereas EK-399 (0.1-3 mg/kg) only partially substituted for morphine in rats trained with morphine. EKC (0.01-0.1 mg/kg), a kappa-opioid receptor agonist, partially substituted for EK-399, and EK-399 (0.1-3 mg/kg) partially substituted for EKC. NANM (0.3-10 mg/kg), a sigma-receptor agonist, partially substituted for EK-399, but EK-399 (0.1-3 mg/kg) did not substitute for NANM. These results suggest that the discriminative stimulus effect of EK-399 in rats mainly involves mu-opioid receptor-mediating action and also involves, to a lesser extent, other receptor (probably delta-opioid receptor)-mediating actions.

Animals↗
PubMed2003

Generalization in response to mate recognition signals.

Females usually exhibit strong and unequivocal recognition of conspecific mating signals and reject those of other sympatric heterospecifics. However, most species are allopatric with one another, and the degree to which females recognize mating signals of allopatric species is more varied. Such mating signals are often rejected but are sometimes falsely recognized as conspecific. We studied the dynamics of mate recognition in female túngara frogs (Physalaemus pustulosus) in response to a series of calls that were intermediate between the conspecific and each of five allopatric-heterospecific calls: two that elicited recognition from females in previous studies and three that did not. This study shows that females perceive variation in allopatric mating signals in acontinuous manner with no evidence of perceptual category formation. The strength of recognition is predicted by how different the target stimulus is from the conspecific call within a series of calls. But the differences in recognition responses among call series are not predicted by the similarity of the call series to the conspecific call. The latter result suggests that the strength of recognition of allopatric signals might be influenced by processes of stimulus generalization and past evolutionary history.

Acoustic Stimulation↗
PubMed2002

Extended amygdala and emotional salience: a PET activation study of positive and negative affect.

Functional neuroimaging studies have implicated amygdaloid and basal forebrain regions, including sublenticular extended amygdala (SLEA), in the mediation of aversive emotional responses. However, it is not clear whether SLEA responds to 'aversiveness' or to general stimulus salience. We predicted that both pleasant and aversive stimuli would activate this region. Using [(15)O] water PET, we studied 10 healthy subjects while viewing pleasant, aversive, neutral, and blank images. Each subject underwent eight scans, which were processed and averaged with standard statistical methods. Both positive and negative stimuli activated regions in SLEA. Both positive and negative content activated the visual cortex, relative to neutral content. Aversive stimuli deactivated the left frontal pole, relative to positive and neutral stimuli. These findings demonstrate that both positive and negative emotional content evokes processing in the sublenticular/extended amygdala region, suggesting that this region is involved in general emotional processing, such as detection or attribution of salience.

Adolescent↗
PubMed1970

An analysis of generalized imitation.

An experimenter presented English words to three intermediate-level children and reinforced accurate imitation of these words. The experimenter also presented novel Spanish words, but the imitation of these words was never experimentally reinforced. One subject quickly ceased performing non-reinforced imitative responses. The other two subjects were exposed to a series of conditions designed to facilitate discrimination. Upon observing the first subject for one session they immediately ceased imitating Spanish demonstrations. For all three subjects, when reinforcement was delivered for responses other than imitation, all imitative responses eventually ceased. When reinforcement was reintroduced for English imitations there was an immediate resumption of such responses to their previous 100% level. The occurrence of non-reinforced imitations in this and previous studies was discussed as being a function of one or combination of four variables: (1) similarity acquiring conditioned reinforcing properties, or (2) instructional, (3) coincidental, or (4) conditional stimulus generalization.

Journal Article↗
PubMedDate not supplied

Treating selective mutism in a paediatric rehabilitation patient by altering environmental reinforcement contingencies.

Selective mutism is a disorder which can cause severe social and academic impairment, and for which a wide variety of treatment approaches have been used, with varying degrees of success. Selective mutism can be conceptualized as the lack of generalization of a class of operant responses (e.g. audible and comprehensible verbalizations) across environmental contexts. The rehabilitation hospital setting, in which the patient is seen daily by multiple people in multiple settings, is particularly well-suited for implementing a systematic behavioural intervention to establish verbal behaviour and simultaneously reinforce its generalization. Data are presented on a 7-year-old female admitted to a rehabilitation hospital following orthopaedic surgery, who met the DSM-IV diagnostic criterion for selective mutism. Additional medical diagnoses included cerebral palsy, microcephaly, and mild mental retardation. A behavioural programme was developed and implemented to reinforce differentially first any communication, then verbal communication across staff and settings. Results were evaluated using a modified multiple baseline across settings design, and demonstrate that verbal, written, and tangible reinforcement effectively increased verbal behaviour where it previously rarely occurred. Results are discussed in terms of the relationship between selective mutism, social phobia and related disorders. The theoretical roles of behavioural phenomena (discriminative stimuli, stimulus generalization) in the development and treatment of these disorders are discussed.

Behavior Therapy↗
PubMed1982

Discriminative stimulus effects of N-substituted analogs of phencyclidine in rhesus monkeys.

In daily sessions of a two-lever, discrete-trial, food-reinforced procedure, rhesus monkeys were trained to discriminate between subcutaneous injections of ketamine (1.0 or 1.8 mg/kg) and control injections. In tests of stimulus generalization, cumulative doses of drugs were administered in single sessions and either control- or ketamine-appropriate responding produced food. Ketamine (1.8 and 3.2 mg/kg) and phencyclidine (0.32 mg/kg) produced an average of more than 90% ketamine-appropriate responding. In contrast, d-amphetamine, atropine, chlorpromazine, codeine, diazepam and quipazine, tested at doses up to and including those that markedly reduced response rates, produced exclusively control-appropriate responding. Dose-related ketamine-appropriate responding was produced by each of ten 1-phenylcyclohexylamines, the potencies of which varied with the length, electronegativity, and number of N-alkyl chains present. The most potent analog of phencyclidine, N-ethyl-1-phenylcyclohexylamine, was approximately equipotent with phencyclidine. These data are consistent with previous reports that the discriminative stimulus effects produced by phencyclidine are representative of a unique class of drugs, and that alkyl substitutions in the region of the piperidine ring alter the potency, but not the characteristic pharmacological activity, of the resulting analogs. The potencies of some of these analogs compared to phencyclidine in rhesus monkeys, however, differed from their relative potencies in rodents. Thus, there appear to be species differences in the role of the nitrogen pharmacophore of these compounds in producing phencyclidine-like behavioral effects.

Animals↗
PubMed2004

Call recognition in the bullfrog, Rana catesbeiana: generalization along the duration continuum.

Male bullfrogs emit multicroak, quasiharmonic advertisement calls that function in mate attraction and neighbor recognition. The degree of variability of acoustic features in these calls can influence perceptual decisions by conspecific receivers. Analysis of duration of individual croaks in spontaneous advertisement calls of a sample of males shows considerable intraindividual variability in this feature, even within short chorusing bouts. The influence of this intraindividual variability on behavior was examined in a series of evoked calling experiments. When presented with synthetic calls whose croak durations varied over the range of the natural variability in this feature, males responded similarly to intermediate and long duration croaks, but significantly less to short duration croaks. When presented with playbacks of calls with croak durations outside the natural range of variability, males again responded significantly less to shorter durations. The response gradient for duration is thus asymmetrical, with stimuli at the shorter end of the continuum evoking fewer responses than stimuli at the longer end. This asymmetry may be related to the biological demands of rejecting perception of heterospecific advertisement calls, and of mediating appropriate responses to conspecific aggressive calls. The shape of the response gradient for duration may reflect a process of stimulus generalization.

Analysis of Variance↗
PubMed1991

Discriminated taste aversion with a 5-HT(1A) agonist measured using saccharin preference.

Rats were trained to discriminate the stimulus properties of the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.4mg/kg i.p.) versus saline, using a discriminated taste aversion procedure. Tests of stimulus generalization and drug substitution were conducted using two-bottle choice tests between saccharin and water. Rats that received pairings of 8-OH-DPAT with LiCl demonstrated significant reductions of saccharin preference when administered 8-OH-DPAT at doses of 0.1mg/kg or higher. 8-OH-DPAT did not alter saccharin preference significantly in controls that did not receive LiCl injections. Other drugs with high affinity for 5-HT(1A) receptors, such as the azapirones gepirone, ipsapirone and buspirone, produced selective reductions of saccharin preference in rats trained to discriminate 8-OH-DPAT from saline but not in controls. Three drugs with low affinity for 5-HT(1A) receptors, the benzodiazepine anxiolytic diazepam, d-amphetamine, and a common metabolite of the azapirones 1-(2-pyrimidinyl) piperazine (1-PP) altered fluid intake significantly but failed to produce significant changes in saccharin preference in either the discrimination or control groups. This study indicates that two-bottle preference tests can be used to measure the stimulus properties of 8-OH-DPAT trained using a discriminated taste aversion procedure, because the stimulus effects of drugs, measured using saccharin preference, can be separated from the nonspecific effects of drugs on fluid consumption.

Journal Article↗
PubMed1988

Sleep and memory.

Generally sleep is considered a time of amnesia. It is not uncommon for an individual to experience 8 h of sleep and have no memory for events during that time. Similarly, a substantial proportion of the population has no memory for dreams that occurred during the night, despite the fact that the literature on awakening during rapid eye movement (REM) sleep clearly shows that individuals normally have four to six "dream experiences" a night. Research on this issue seems to indicate that the lack of memory cannot be explained by the organisms' inability to perceive stimuli. The data indicate that although perceptual thresholds are elevated, organisms can clearly perceive stimuli, and, in fact, can discriminate between them during sleep. The amnesia also cannot be explained by a defect in long-term memory, as studies have indicated that stimuli put into the memory during wakefulness are more efficiently retrieved after a sleep period than after a comparable period of wakefulness. The most likely explanation for the amnestic property of sleep seems to be the inability of organisms to transfer information from short-term memory to long-term memory during sleep. There are several sources of evidence to support this hypothesis. First, the probability of remembering a stimulus given during wakefulness is related to the proximity of sleep onset to the stimulus. Generally, information put into the system within 5 min of sleep onset is lost from memory. Secondly, disorders of excessive daytime somnolence which cause individuals to have frequent microsleeps are often associated with complains of memory problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1994

Behavioral specializations of SI and SII cortex: a comparative examination of the neural logic of touch in rats, cats, and other mammals.

In what ways do passive touch and active touch require particular properties of cortical physiology? Because it is not easy to make predictions "bottom up" from neurophysiology and anatomy to behavior, there have been surprises in studying behavioral deficits following selective ablations of SI versus SII. For example, in earlier research on cats, unilateral ablation of SI unexpectedly had no effect on passive touch but did cause contralateral losses in posture and movement; it was ablation of SII plus subjacent cortex that led to contralateral losses in passive touch. In contrast, in a recent experiment with rats unilateral ablation of either SI or SII caused contralateral losses both in touch and postural reflexes. Some of the literature on dogs, monkeys, and humans suggests similarities with cats. To better understand these comparative findings, the following theoretical factors are considered: the degree of diffuseness versus specificity in brain input-output relations demanded or permitted by a behavior, the spatial and temporal scales of a behavior, the species' degree of encephalization, the need for stimulus generalization or functional equivalence of movements, and the relative sizes and sensitivities of different parts of the body. Hypotheses are also offered about why the evolution in rats of shortened forelimbs and increased vibrissal function may have entailed a peculiar compromise between active and passive touch and between functions of SI and SII.

Animals↗
PubMed1994

Reasoning in middle childhood: a dynamic model of performance on transitivity tasks.

An overview of the models and data relevant to children's transitive reasoning is provided. We propose a new conceptual framework, one which is embedded in a dynamic model that accounts for children's failures to reason transitively. It is assumed that rather than reasoning in a transitive manner, children often encode both relational and absolute stimulus information and use stimulus generalization as a transfer mechanism. The model is applied to new and extant data. The model provides an adequate and parsimonious account of children's failures on these tasks. We conclude that progress in understanding children's reasoning is dependent on operationalizing constructs in formal models so that assumptions can be evaluated and rejected.

Age Factors↗
PubMed2001

Acute stress rapidly and persistently enhances memory formation in the male rat.

Previous studies, as well as the present one, report that acute exposure to intermittent tailshocks enhances classical eyeblink conditioning in male rats when trained 24 h after stressor cessation. In Experiment 1, it was determined that the facilitating effect of stress on conditioning could also be obtained in response to a stressor of acute inescapable swim stress but not inescapable noise or the unconditioned stimulus of periorbital eyelid stimulation. These selective responses arose despite comparable enhancements of the stress-related hormone corticosterone in response to tailshocks, periorbital eyelid stimulation, noise stress, and supraelevation in response to swim stress. Although corticosterone is necessary for the enhanced learning in response to stress (Beylin & Shors, 1999), these results suggest that it is not sufficient. In addition, the results suggest that the enhancement is not dependent on common characteristics between the stressor and the conditioning stimuli (stimulus generalization). In Experiment 2, it was determined that the facilitating effect of the stressor on conditioning occurs within 30 min of stressor cessation. Thus, the mechanism responsible for facilitating memory formation is rapidly induced as well as persistently expressed. In Experiment 3, it was determined that exposure to the stressor does not enhance performance of the conditioned response after the response has been acquired. Thus, exposure to the stressor enhances the formation of new associations rather than affecting retention or performance of the motor response. These studies extend the circumstances under which stress is known to enhance associative learning and implicate neural mechanisms of memory enhancement that are rapidly induced and persistently expressed.

Acute Disease↗
PubMed1977

Differential haloperidol effect on two indices of fentanyl-saline discrimination.

Using a discrete-trial, two-lever, food-reward discrimination learning paradigm, we trained rats (n = 6) to discriminate 0.04 mg/kg fentanyl (s.c. t-30') from saline. Stimulus generalization experiments with an adequate dose range (0.01-0.04 mg/kg) of fentanyl revealed that the ED50 value for drug lever selection is 0.02 mg/kg, irrespective of whether the animals were pretreated (s.c., t-60') with either saline or 0.08 mg/kg haloperidol. With increasing doses of the haloperidol-fentanyl combination, the percentage of total responding on the selected lever progressively decreased, and reached the 50% level at the highest drug combination. It is concluded that this percentage is heavily contaminated by factors unrelated to the discrimination condition being studied; these factors seem to invalidate this percentage as a discrimination index under experimental conditions (e.g., behaviorally toxic doses of drugs) where they are likely to operate. The use of response selection as a discrimination index in drug discrimination research is further argued.

Animals↗