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H Dai

Publications and source records attributed to H Dai.

At least 109 records · Page 6Linked to original sources

The NMDA receptor and cocaine: evidence that MK-801 can induce behavioral sensitization effects.

Antagonism of the NMDA receptor with MK-801 is considered to be an effective pharmacologic manipulation to prevent the development of sensitization effects to drugs such as cocaine. The present study investigated this issue by comparing the behavioral response of separate groups of rats to three treatment cycles of either saline, 0.1 mg/kg MK-801, 10 mg/kg cocaine, or combined MK-801-cocaine (0.1/10 mg/kg). The treatments were spaced 1 week apart and were preceded by two nondrug baseline tests. In the first test cycle, the four groups had equivalent activity levels in the two nondrug tests. In the first drug test only the MK-801-cocaine group exhibited hyperactivity. By the third drug test, the MK-801-cocaine group exhibited an enhanced hyperactivity and the MK-801 group became hyperactive. Thus, behavioral drug sensitization developed but only with groups treated with MK-801. Antagonism of the NMDA receptor under some circumstances can be a highly effective treatment for the induction of behavioral sensitization effects.

Animals↗

A new methodological approach to the study of habituation: the use of positive and negative behavioral indices of habituation.

This report details a new method to measure habituation in an open-field. In addition to the measurement of spontaneous locomotor activity, time spent per visit to the center zone (CZ) is also measured. Critically, a small object is placed in the CZ to modulate an animal's investigatory response. When an animal is first exposed to the open-field, the presence of the object does not affect the duration of its visits to the CZ but, if the animal is given one additional 10-min exposure to the open-field, then the presence of the object substantially increases the duration of its visits to the CZ. The presence of the object, however, has no effect on the rat's locomotor activity. Thus, habituation could be observed by two different measures: a decrease in locomotor activity and an increase in an animal's investigatory response to a stimulus object. A basic problem with a reliance solely upon a decrease in locomotor activity to measure habituation is that it represents a negative change in behavior. The present method circumvents this shortcoming by incorporating a positive behavioral measure of habituation in conjunction with the measurement of locomotor activity. This modification of the open-field test offers substantial utility for studies of neurotoxicology and memory because one can assess concurrently treatment effects on motor activity, attention to an object and memory.

Animals↗

Time course effects of MK-801: the relationship between brain neurochemistry and behavior.

Separate groups of rats were given saline or MK-801 treatments (0.3 mg/kg) and tested for locomotion activity levels for 10 min at 30, 60, and 120 min postinjection. At each postinjection time interval the MK-801 rats exhibited a marked hyperactivity that was unchanged across the three postinjection intervals. Ex vivo biochemical assays were performed to assess the neurochemical effects of MK-801 at each injection interval. In the striatum, a marked increase in dopamine metabolism was observed in the 120 injection group, but, otherwise, no other changes in striatum were detected. In contrast, a significant increase in dopamine metabolism was observed after 30 min in the medial prefrontal cortex, and this effect persisted across all postinjection intervals. At 120 min, however, the biochemical impact of the MK-801 treatment on medial prefrontal cortex broadened to include a decrease in purine metabolism and norepinephrine. Serotonin metabolism was unaffected in striatum or medial prefrontal cortex across all injection intervals, and there was no effect of MK-801 on plasma corticosterone levels.

Animals↗

L-DOPA metabolism in cortical and striatal tissues in an animal model of parkinsonism.

Rats with unilateral 6-hydroxydopamine lesions of the midbrain tegmentum were treated with 25 mg/kg L-DOPA methyl ester/2 mg/kg carbidopa. The effects of the L-DOPA treatment upon serum, neocortical, and striatal L-DOPA and 3-O-methyl dopa (3-OMD) concentrations were measured. The highest L-DOPA and 3-OMD concentrations were obtained in the serum and in a ratio of approximately 2:1. In the brain, there was a uniform distribution of 3-OMD but L-DOPA concentrations were highly nonhomogeneous. Regression line equations for the statistically significant correlation coefficients between L-DOPA and tissue dopamine concentrations suggested that L-DOPA generated 50-60 times as much dopamine in the intact striatum as in cortex. The regional variation of L-DOPA concentration appears related to the capability of the brain tissue to generate and store dopamine from L-DOPA. In addition, the findings suggest that the behavioral ineffectiveness of L-DOPA in intact animals is related to its capacity to transform L-DOPA to tissue bound dopamine.

Animals↗

A two-filter model for frequency discrimination.

In this paper, we explore a two-filter model, the simplest version of multi-channel models for frequency discrimination of simple tones. According to this model, frequency discrimination is based on a change in the relative output levels of two auditory filters, one centered below and the other above the frequency of the tone. This idea can explain the experimental results that frequency discrimination is relatively unaffected by randomization of stimulus level. Moreover, it suggests a close relationship between the ability of listeners to perform frequency discrimination of simple tones and spectral-shape discrimination of two-tone complexes. The ability of three listeners to perform these two tasks was measured at six frequencies (from 0.25 to 8 kHz). The results from the spectral-shape-discrimination task were used to predict frequency-difference limens. There was a high correlation between obtained and predicted values.

Acoustic Stimulation↗

Influence of hemodialysis membranes on gene expression and plasma levels of interleukin-1 beta.

Plasma levels of interleukin-1 beta (IL-1 beta) were measured in 10 normal subjects, in 11 nondialyzed end-stage renal failure (ESRD) patients, and in 22 hemodialysis (HD) patients. Of the HD patients, 7 were dialyzed with Cuprophan (CU), 7 with polymethylmethacrylate (PMMA), and 8 with polysulphone (PS) dialyzers. In normal controls, nondialyzed ESRD patients, and HD equipped with CU, PAMM, and PS dialyzers, plasma levels of IL-1 beta were 10.73 +/- 5.24 pg/ml, 9.97 +/- 3.61 pg/ml, 13.17 +/- 4.04 pg/ml, 15.16 +/- 6.16 pg/ml, and 13.96 +/- 5.47 pg/ml, respectively. There were no statistically significant differences among the groups (p > or = 0.05). In contrast, the gene expression of IL-1 beta for peripheral blood mononuclear cells (PBMC) by in situ hybridization showed differences among the groups. The gene for IL-1 beta for PBMC appears in HD equipped with different membranes, but not in cases of nondialyzed uremic patients and normal subjects. With computer imaging analysis, we carried out quantitative analysis of cells in in situ hybridization with an area of positive spots to an area of total cells. In HD with CU, PMMA, and PS, the results were 10.64 +/- 1.07, 3.34 +/- 0.74, and 3.27 +/- 0.64%, respectively. The levels of IL-1 beta gene expression in CU were higher than that in PMMA or PS. There were statistically significant differences (p < or = 0.001) between CU and PMMA or PS and no significant difference between the PMMA and PS (p > or = 0.05). We suggest measuring the gene expression of cytokines for PBMC and which may be better than measuring cytokine levels only for investigating the blood compatibility of dialyzers, which may help in understanding chronic complications of the dialysis procedure.

Adult↗

Discriminating coherence in spectro-temporal patterns.

This study examined the ability of trained listeners to discriminate coherent components in randomly varying spectral patterns. In each observation interval, the listener was presented with a sequence of bursts of multitone complexes having a fixed number of tones (m) in each burst. In the standard interval, the frequency of each tone in every burst was chosen randomly between 200 and 5000 Hz. In the signal interval, the frequencies of n tones were repeated throughout the burst sequence while the remaining m-n tones were chosen at random. The n tones were coherent in the sense that they were perceived as "sticking together" to form a pattern. The listener's task was to discriminate which burst sequence contained the n components. The results indicated that discrimination improved with increasing n/m, with increasing number of bursts per interval, and declined as the coherent components were increasingly perturbed in frequency. Further, for a fixed value of the ratio n/m discriminability was relatively independent of m. A model incorporating multichannel filtering and an optimum decision rule was reasonably successful in accounting for the experimental results.

Adult↗

Detecting signals of unexpected or uncertain durations.

Expectation of signal duration influences the signal detectability. This is demonstrated in two experiments in which percent correct was measured for both tonal and noise signals whose durations were either unexpected or uncertain. In both experiments, the signal at each duration was set to have a d' of about 1.5 when that duration was presented alone and expected. When the six subjects were led to expect a short- or a long-duration signal using the probe-signal method, the detectability of signals decreased to near chance as the signal duration deviated from the expected value (experiment 1). When the subjects were led to expect a range of durations, the detectability was only slightly worse than when each signal was presented alone (experiment 2). Those results suggest that listeners adjust their temporal-integration intervals according to the demand of the specific task. Finally, the results obtained with the noise signal were analyzed using the multiple-look model and a modified energy-detector model. Assuming that the integration interval is matched to the expected signal duration, both models predict the detection of signals having unexpected durations reasonably well. Both models, however, fail to predict the small effect of duration uncertainty.

Audiometry, Pure-Tone↗

On measuring psychometric functions: a comparison of the constant-stimulus and adaptive up-down methods.

Psychometric functions were obtained using the conventional constant-stimulus method and an adaptive up-down method, for both computer-simulated and human observers. Except when the stimuli are closely placed, psychometric functions obtained with the adaptive method are as accurate as those obtained with the constant-stimulus method. Empirically, the adaptive method has some potential advantages owing to its ability to automatically concentrate the trials within the dynamic range of the psychometric function. It needs no pilot measurements for setting the signals as required by the constant-stimulus method. Furthermore, following a marked change in the underlying psychometric function, the distribution of the trials is automatically readjusted. Thus, on the basis of empirical considerations, the adaptive method is a better choice than the constant-stimulus method for measuring psychometric functions.

Auditory Perception↗

[Use of perfluorodecalin in giant retinal tear retinal detachment surgery].

Perfluorodecalin is used for the treatment of 11 eyes with giant retinal tear retinal detachment surgery. Perfluorocarbon liquids can be used as an operative hydrodynamic tool during vitreous surgery. The high specific gravity of perfluorocarbon liquids allows an easy unfolding of the inverted flap and flattening of the retina, displacing the subretinal fluid and stabilizing the retina for membrane peeling. Endophotocoagulation may be performed under optimal visual condition. The success rate was 81.8% (9/11). The retina failed to reattach in patients with advanced proliferative vitreoretinopathy. The surgical techniques were discussed.

Adolescent↗

Differentiation of motor inactivation from movement asymmetry effects in an animal model of hemi-parkinsonism.

Rats subjected to unilateral 6-hydroxydopamine lesion of the pars compacta of the substantia nigra sustained a wide range of dopamine (DA) loss in the neostriatum. Residual DA levels of < 50% resulted in behavioural impairments which correlated with the degree of DA denervation, whereas no such effects occurred with residual DA levels of > 50%. Within 1 week after surgery the effects of the lesion on motor activation recovered whereas movement asymmetrics exhibited no recovery. In addition, movement asymmetry effects were not correlated with motoric inactivation effects. This finding indicates that dopamine denervation of the neostriatum disrupts sensory/motor integration and attentional processes rather than motor activation.

Animals↗

Cocaine stimulant effects vary with cocaine levels in medial prefrontal cortex.

Rats treated with 10 mg kg-1 cocaine exhibited hyperlocomotion. Individual variation in the magnitude of this response was not correlated with serum cocaine concentration. Brain cocaine concentration, particularly in the medial prefrontal cortex, was highly correlated with the cocaine-induced locomotor stimulant effect. These findings indicate that variation in the uptake of cocaine into the brain is a critical variable in determining individual variation in its stimulant effects.

Animals↗

'Priming' enhances the relationship of striatal L-dopa concentration to behavior.

Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were exposed to L-DOPA treatments, 25 mg kg-1 L-DOPA methyl ester/2 mg kg-1 carbidopa, or to saline. Fourteen days later, both sets of animals were tested with the L-DOPA/carbidopa treatment. The L-DOPA pre-exposed animals exhibited behavioral sensitization as indexed by a higher frequency of contralateral rotations. Although striatal L-DOPA and HVA concentrations were equivalent in the two groups, the L-DOPA treatment induced a 10 fold variation in the range of L-DOPA concentrations in the 6-OHDA striatum in both sets of animals. Importantly, significant correlations between striatal L-DOPA concentration and behavior were obtained only for the L-DOPA pre-exposed animals.

Animals↗

The NMDA antagonist MK-801 can impair attention to exteroceptive stimuli.

Using a modified open-field method, we assessed the effects of MK-801 (0.01 to 0.3 mg/kg) on locomotion and on attention to a stimulus object located in a computer-generated central zone (CZ). The CZ comprised 1/9 of the open-field floor area and was monitored independently from the rest of the area. Intermittently, a 4 x 4 x 2 cm block was placed in the CZ. In 10-min trials, non-drug tests showed that the presence of the stimulus object repeatedly and consistently increased the rats' visit duration in the CZ as compared with tests when the object was absent. Locomotor activity and entries to the CZ were unaffected by the object. MK-801 induced dose dependent hyperlocomotion and increased CZ entries and, most important, a dose dependent decrease in the animal's response to the stimulus object in the CZ. The present investigation suggests that MK-801 impacts upon two major functions; (a) a blockade of processing of attentional information from the external world and (b) activation of locomotor response systems. These findings are consistent with the hypothesis that blockade of glutamate neurotransmission by MK-801 impairs the flow of information from the external world to response mechanisms in the striatum. The present study also suggests that MK-801's potential as a therapeutic agent for motoric activation in the treatment for Parkinson's disease would be contraindicated by its disruptive influence upon attention processing functions.

Animals↗

Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy control mechanism.

The study characterizes the process of sensitization induced by intermittent administrations of quinpirole (0.5 mg/kg) in rats in a large open field. Sensitization was found to be self-limiting, with all measures of behavior reaching a plateau after the tenth twice-weekly injection. Kinetics of sensitization were a simple hyperbolic function of the number of drug injections for some measures (speed of locomotion, length of locomotor bouts) but showed positive co-operativity for others (distance travelled, duration of locomotion, frequency of stops, route stereotypy), suggesting potentiation of the effect by preceding injections. The pace of sensitization varied for different behaviors: locomotor speed changed fastest in the early portion of chronic treatment; stereotypy of route changed primarily during the late phase; mouthing did not sensitize. Sensitization evolved by a cascade of changes that included: advancing the onset of locomotor activation; prolonging the duration of locomotion; establishing new maxima of observable responses; altering the mode of locomotion; raising speed, rate and length of locomotor bouts; and increasing stereotypy of travel. These observations do not substantiate the prediction that development of behavioral sensitization is associated with emergence of disorganized activity and/or fractionation of response chains. Instead, it is proposed that development of sensitization may represent a build-up and strengthening of performance, reflecting enhanced central control of energy expenditure stimulated by repeated injections of quinpirole. Furthermore, it is suggested that for at least one response, the maximum observable amount of locomotion, development of sensitization requires only D2 stimulation, independent of D1 tone.

Amphetamine↗

L-dopa induced increases in brain uric acid in an animal model of Parkinson's disease: a relationship to behavioral activation.

Rats with severe unilateral dopamine denervation (> or = 95% dopamine deficit), produced by intracerebral injection of 6-hydroxydopamine (6-OHDA) into the ventral tegmentum nigrostriatal dopamine neurons, were administered 25 mg/kg L-dopa (3,4-dihydroxyphenylalanine) methyl ester/2 mg/kg carbidopa. The neurochemical effects of the L-dopa treatment on uric acid in the cortex and striatum of the intact and 6-OHDA hemisphere were measured. In comparison to saline animals, uric acid concentrations in brain were increased in the L-dopa treated animals. There were no interhemispheric differences in the uric acid concentrations either in the L-dopa or in the saline treated animals. Interhemispheric differences were, however, observed in terms of the correlations obtained between L-dopa and uric acid concentrations in the intact vs. the 6-OHDA hemisphere. Statistically significant correlation coefficients were found in the striatal and cortex samples obtained from the 6-OHDA hemisphere. Furthermore, high correlation coefficients were observed between contralateral rotation frequencies and uric acid concentrations in the cortex and striatum of the 6-OHDA hemisphere. In contrast, only low and statistically non significant correlations were observed in the tissue samples obtained from the intact hemisphere. These observations suggest that L-dopa activation of the dopamine supersensitive receptors of the DA denervated hemisphere and the associated metabolism of purines with high energy phosphate bonds (e.g. ATP and GTP) increases uric acid as an end-product of purine metabolism. These findings are consistent with other findings indicating that uric acid in the brain can provide an index of metabolic activation in brain tissue.

Animals↗

Effects of dose and interdose interval on locomotor sensitization to the dopamine agonist quinpirole.

To assess whether the interval between injections affects the course of locomotor sensitization to quinpirole, groups of rats were injected every 2, 4, or 8 days with quinpirole (0, 0.025, 0.25, 0.5, and 2.5 mg/kg; n = 222) and their locomotor activity monitored after each injection for a total of 10 tests. Results indicate that the number of drug injections, rather than the interval between them, predominantly controls the development of locomotor sensitization to quinpirole. It is suggested that this may reflect a rapid induction but slow decay time for a response-enhancing factor stimulated by each injection of quinpirole, and that the effects of this putative factor are cumulative but saturable.

Animals↗