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At least 1,531 records · Page 85Linked to original sources
PubMed1996

Separate neural substrates mediate the motivating and discriminative properties of morphine.

A previous study (T. V. Jaeger & D. van der Kooy, 1993) has implicated a visceral and taste region (parabrachial nucleus), but not mesolimbic dopamine terminal fields (nucleus accumbens), as a substrate for opiate discriminative effects. The authors now show that (a) morphine's discriminative effects in the parabrachial nucleus (PBN) require the activation of opiate receptors; (b) in rats trained to discriminate morphine from saline, infusions of morphine into the ventral tegmental area (VTA) do not generalize to the systemic training condition; (c) infusions of morphine into the PBN, but not the VTA, serve as a stimulus for the acquisition of discrimination learning; and (d) morphine applied to the VTA, but not the PBN, is motivating. The data show that the motivating and discriminative effects of morphine are processed separately by the brain. Further, discriminative drug effects are neither necessary nor sufficient for opiate motivational effects.

Animals↗
PubMed1986

The discriminative stimulus and subjective effects of d-amphetamine, phenmetrazine and fenfluramine in humans.

The discriminative stimulus (DS) and subjective effects of d-amphetamine (AMP), phenmetrazine (PMT) and fenfluramine (FFL) were studied in a group of normal healthy adults. Subjects (N = 27) were trained to discriminate between placebo and 10 mg AMP (PO). Fourteen of the subjects (discriminators) reliably learned the discrimination, whereas the other 13 did not. Nearly all discriminators labelled AMP as a stimulant, and AMP, relative to placebo, increased ratings of drug liking and general activity level, and produced typical stimulant-like subjective effects, as measured by the Profile of Mood States, the Addiction Research Center Inventory, and a series of visual analog scales. The discrimination accuracy of discriminators increased as a function of hour after drug ingestion, as did analog ratings of how certain subjects were that their discrimination responses were correct. Discriminators were tested with doses of PMT (25 and 50 mg) and FFL (20 and 40 mg) to determine whether the DS properties of these drugs would substitute for those of AMP. Both doses of PMT consistently substituted for AMP, and PMT produced subjective effects very similar to those of AMP. Conversely, neither dose of FFL consistently substituted for AMP, and FFL produced essentially no subjective effects. These findings are consistent with results from discrimination studies with other species, and provide further evidence of the validity of this procedure for studying the DS properties of drugs in humans.

Adult↗
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↗
PubMed1995

Influence of local environmental olfactory cues on place learning in rats.

The aim of the present study was to assess the influence of local environmental olfactory cues on place learning in rats. We developed a new experimental design allowing the comparison of the use of local olfactory and visual cues in spatial and discrimination learning. We compared the effect of both types of cues on the discrimination of a single food source in an open-field arena. The goal was either in a fixed or in a variable location, and could be indicated by local olfactory and/or visual cues. The local cues enhanced the discrimination of the goal dish, whether it was in a fixed or in a variable location. However, we did not observe any overshadowing of the spatial information by the local olfactory or visual cue. Rats relied primarily on distant visuospatial information to locate the goal, neglecting local information when it was in conflict with the spatial information.

Animals↗
PubMed1984

Relative contributions of SII and area 5 to tactile discrimination in monkeys.

Rhesus monkeys with ablations of either the second somatosensory cortex (SII) or of the superior parietal lobule (area 5) were tested on a battery of tactile discrimination tasks in order to help determine which of these areas might constitute part of a postulated cortico-limbic tactile processing pathway. Monkeys with ablations of SII were severely impaired on both texture and shape discrimination learning and had markedly elevated size and roughness discrimination thresholds relative to control animals. By contrast, monkeys with area 5 lesions were impaired only on roughness thresholds, and these were elevated only moderately. Although more severe tactile deficits following lesions of area 5 have been reported previously, they were found in the present study only when the area 5 removals were extended slightly rostrally, in a third operated group, to include the posteromedial part of the hand representation of area 2. These results are consistent with the suggestion that SII, but not area 5, is a critical station in a tactile processing pathway that proceeds from the primary somatosensory cortex (SI) to the limbic structures of the temporal lobe through links in SII and the insular cortex.

Animals↗
PubMed2006

The role of temporal generalization in a temporal discrimination task.

Two experiments trained rats to discriminate two or three stimulus durations using a temporal discrimination task. A standard peak shift effect was observed when training was administered with short versus long signals in Experiment 1. Both discrimination accuracy scores and the generalization gradients revealed that shorter intervals were discriminated more accurately, which may be due to the scalar property of timing. In Experiment 2, three signals (short, medium, and long) were associated with three different responses, or two of the intervals were associated with one response (short and long or short and medium) and the other interval with a different response. Here, the short/medium versus long discrimination was learned most readily of the three tasks. The results of both experiments indicated a strong contribution of learning of individual durations combined with scalar generalization gradients, but Experiment 2 indicated that categorical encoding of durations may have also been operating.

Animals↗
PubMed1998

Learning in year-old female autoimmune BXSB mice.

BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease. Approximately 40-60% of these animals show ectopic clusters of neurons in Layer I of cortex similar to those found in postmortem analyses of human dyslexics, and all exhibit an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans. The expression of immune disease in the BXSB strain, unlike in humans, is more severe in males than females. Most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age, when the BXSB females (unlike the male BXSB and female and male NZBs) are not yet showing high titers of autoantibodies associated with their lupus-like form of autoimmune disease. This study examined the behavior of BXSB females at an age subsequent to autoimmune disease onset. When contrasted with younger animals, year-old BXSB females showed good learning behavior, with no differences in Lashley maze learning and remarkably good performance in a visual discrimination learning task. These results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease. Results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in Lashley maze learning. Animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures. These findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals.

Age Factors↗
PubMed1999

BXSB mice can learn complex visual pattern discriminations.

To determine if mice could perceive differences among several complex black/white patterns, a water version of a radial-arm maze was modified into a T-maze. BXSB mice were able to discriminate between multiple pairs of stimuli.

Analysis of Variance↗
PubMed2006

Aripiprazole as a potential pharmacotherapy for stimulant dependence: human laboratory studies with d-amphetamine.

Amphetamine and cocaine dependence present significant public health concerns, yet no broadly effective pharmacotherapy for stimulant dependence has been developed. Two human laboratory studies are reviewed that tested the ability of aripiprazole, a novel antipsychotic with partial agonist activity at D2 dopamine receptors, to alter the behavioral effects of stimulants using d-amphetamine as a model agent. In each of these experiments, volunteers learned to discriminate 15 mg d-amphetamine (i.e., > or =80% drug-appropriate responding over 4 consecutive sessions). The effects of a range of doses of d-amphetamine (0, 2.5, 5, 10, and 15 mg) were then tested alone and following pretreatment with aripiprazole (20 mg in Experiment 1; 10 mg in Experiment 2). In Experiment 1, aripiprazole (20 mg) attenuated the discriminative stimulus and many of the subject-rated effects of amphetamine. Aripiprazole alone produced performance decrements. To determine whether a lower dose of aripiprazole would also attenuate the behavioral effects of d-amphetamine without impairing performance, Experiment 2 was conducted. Aripiprazole (10 mg) failed to alter the discriminative-stimulus effects but attenuated some of the subject-rated effects of d-amphetamine. This dose of aripiprazole did not impair performance. The results of these experiments indicate that aripiprazole may have clinical utility in treating stimulant dependence. Future human laboratory research should better model the clinical use of aripiprazole by examining the effects of chronic aripiprazole combined with either methamphetamine or cocaine in dependent individuals. A large-scale clinical trial is also needed to evaluate the efficacy of aripiprazole for the treatment of stimulant dependence.

Adult↗