Search PubMed⌕ Search

Biomedical subjects

M Y Ho

Publications and source records attributed to M Y Ho.

At least 19 recordsLinked to original sources
PubMed2002

Development and inter-rater reliability of a standardized verbal instruction manual for the Chinese Geriatric Depression Scale-short form.

The Geriatric Depression Scale (GDS) is a common screening tool for elderly depression in Hong Kong. This study aimed at (1) developing a standardized manual for the verbal administration and scoring of the GDS-SF, and (2) comparing the inter-rater reliability between the standardized and non-standardized verbal administration of GDS-SF. Two studies were reported. In Study 1, the process of developing the manual was described. In Study 2, we compared the inter-rater reliabilities of GDS-SF scores using the standardized verbal instructions and the traditional non-standardized administration. Results of Study 2 indicated that the standardized procedure in verbal administration and scoring improved the inter-rater reliabilities of GDS-SF.

Aged↗
PubMed2002

SB-242235, a selective inhibitor of p38 mitogen-activated protein kinase. II: in vitro and in vivo metabolism studies and pharmacokinetic extrapolation to man.

1. Inhibition of p38 MAP kinase has been investigated extensively as a potential therapy for cytokine-mediated diseases such as autoimmune and inflammatory diseases. SB-242235 (1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-methoxy-4-pyrimidinyl) imidazole) is a potent and selective p38 MAP kinase inhibitor; the preclinical pharmacokinetics of SB-242235 have been described previously. The present studies were conducted to describe the in vitro metabolic rates and routes of SB-242235 metabolism, to characterize its in vivo preclinical metabolism, and to use these data to aid in the prediction of the pharmacokinetic behaviour of SB-242235 in man. 2. SB-242235 was metabolically stable in rat, dog, monkey and human hepatic microsomes, isolated hepatocytes and liver slices in vitro. The in vivo preclinical metabolism studies were consistent with the in vitro findings; SB-242235 was minimally metabolized, and was primarily excreted unchanged in the urine (45 and 67% of the administered dose in the rat and monkey, respectively). 3. Allometric scaling using various correction factors predicted that SB-242235 would have low clearance in man with a predicted half-life ranging from 11.5 to 18.7h. This prediction was consistent with the observed mean half-life of 16.4h in the first-in-man study for SB-242235. An allometric scaling method with a correction for interspecies differences in glomerular filtration rate provided the most accurate prediction of the pharmacokinetic behaviour of SB-242235 in humans, although the clinical data also highlight potential difficulties in conducting prospective allometry.

Animals↗
PubMed2001

Selective self-ion/molecule reactions in both external and internal source ion trap mass spectrometers.

Novel results on the selective self-ion/molecule reactions (SSIMR) in both external and internal source ion trap mass spectrometers are demonstrated. Selective self-ion/molecule reaction product ions were produced between the oxygenated and nitrogenated crown ethers. For the oxygenated crown ethers, self-ion/molecule reactions lead to the formation of the protonated ions, adduct ions of fragments ([M + F](+)) and [M + H(3)O](+), while the nitrogenated crown ethers produce [M + H](+), [M + CH](+) and [M + C(2)H(3)](+) ions.

Journal Article↗
PubMed2001

Failure of central 5-hydroxytryptamine depletion to alter the effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on timing performance on the free-operant psychophysical procedure.

RATIONALE: The 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) alters temporal differentiation of behaviour on the free-operant psychophysical procedure, displacing the psychophysical curve to the left, thereby reducing the indifference point T(50). However, it is not known whether this effect of 8-OH-DPAT is mediated by an action of the drug at somatodendritic autoreceptors or at postsynaptic receptors. OBJECTIVE: To compare the effects of 8-OH-DPAT on performance on the free-operant psychophysical procedure in normal (sham-lesioned) rats and in rats whose 5-HTergic pathways had been lesioned by means of intra-raphe injections of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). METHODS: Twelve rats received 5,7-DHT-induced lesions of the median and dorsal raphe nuclei, and twelve received sham lesions. They were trained under the free-operant psychophysical procedure to press two levers (A and B) in 50-s trials, during which reinforcement was provided intermittently for responding on A in the first half and B in the second half of the trial. Percentage responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic psychophysical curves were fitted to the data from each rat for the derivation of timing indices [T(50) (time corresponding to %B=50%) and Weber fraction] following treatment with acute doses of 8-OH-DPAT (25, 50, 100, 200 microg kg(-1), s.c.) and saline (vehicle-alone treatment). Levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline and dopamine were measured in forebrain regions after the completion of the experiment. RESULTS: Under the vehicle-alone condition, the lesioned group displayed a greater propensity for switching between the levers, but T(50) and the Weber fraction did not differ between the groups. In both groups, 8-OH-DPAT shifted the psychophysical curve to the left, significantly reducing T(50) at the 200-microg kg(-1) dose; the effect of 8-OH-DPAT did not differ significantly between the groups. Levels of 5-HT and 5-HIAA in the lesioned group were about 10% of those in the sham-lesioned group; there was no effect of the lesion on catecholamine levels. CONCLUSIONS: The results confirm that 8-OH-DPAT disrupts temporal differentiation in the free-operant psychophysical schedule, reducing the indifference time, T(50). The failure of central 5-HT depletion to alter the effect of 8-OH-DPAT suggests that this effect may be mediated by stimulation of postsynaptic 5-HT(1A) (or possibly 5-HT(7)) receptors rather than somatodendritic 5-HT(1A) autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Examination of the best pressure range for ion/molecule reactions of anthraquinones in an external source ion trap mass spectrometer.

This study outlines some observations of the pressure effect for gas phase ion-molecule reactions of anthraquinone derivatives with dimethyl ether in an external source ion trap mass spectrometer. At the reagent pressure of 7.998 x 10(-2) Pa, formation of the protonated ions, [M + 13]+, [M + 15]+, and [M + 45]+ ions, of anthraquinones can be observed. However, at the pressure of 1.066 x 10(-2) Pa, formation of molecular ions and many fragment ions of the M+. or [M + H]+ ions have been observed. Since the pressure effect is notable within a small range of pressures for many compounds, it is important to draw attention to the use of the ion trap with an external source where other factors such as ion source residence time may play a role. This can also provide some information for better and more careful controls of the reagent pressure in order to obtain fair CI spectra in an external source ion trap mass spectrometer.

Journal Article↗
PubMed2000

Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis.

RATIONALE: It has been proposed that the ascending 5-hydroxytryptaminergic (5-HTergic) pathways are involved in "impulse control". Previous experiments have shown that rats whose 5-HTergic pathways have been destroyed are more liable than intact rats to select a smaller, immediate reinforcer rather than a larger, delayed reinforcer (impulsive choice). However, it remains unclear whether this effect of central 5-HT depletion reflects a change in the rate of time discounting (i.e. a change in the rate at which reinforcers become devalued as a function of delay) or a change in sensitivity to reinforcer size. OBJECTIVE: We examined the effect of central 5-HT depletion on time discounting using a quantitative model of inter-temporal choice (multiplicative hyperbolic model), which enables effects on time discounting to be differentiated from effects on sensitivity to reinforcer size. METHODS: Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press two levers for food-pellet reinforcers in a discrete-trials adjusting-delay schedule. In free-choice trials, selection of lever A resulted in a brief fixed delay (dA) followed by delivery of one pellet; selection of lever B resulted in a longer variable delay (dB) followed by delivery of two pellets; dB was adjusted in accordance with the subject's choices. The value of dA was varied (0.5-8.0 s) in successive phases of the experiment, and the indifference value of dB was determined in each case. RESULTS: In both groups, the indifference value of dB was linearly related to the value of dA, in accordance with the multiplicative hyperbolic model. The lesioned group showed shorter indifference delays than the sham-lesioned group, this being reflected in a parallel displacement of the linear indifference function. In both experiments, the levels of 5-HT and 5-hydroxyindole-acetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. CONCLUSIONS: According to the multiplicative hyperbolic model, parallel displacement of the linear indifference function uniquely specifies a change in time discounting. Thus these results indicate that central 5-HT depletion results in an increase in the rate of time discounting for food reinforcers.

5,7-Dihydroxytryptamine↗
PubMed2000

The effect of d-amphetamine on performance on two operant timing schedules.

RATIONALE: Previous experiments have shown that d-amphetamine disrupts timing behaviour in rats. It has been proposed that d-amphetamine's effects reflect a reduction in the period of the pacemaker of the hypothetical internal clock. However, some studies have obtained conflicting results. OBJECTIVE: To examine the effects of d-amphetamine (0.2, 0.4, 0.8 mg kg(-1) i.p.) on performance on two quantitative timing schedules: a free-operant schedule, in which rats were trained to distribute their responses differentially between two levers during the course of a 50-s trial (free-operant psychophysical procedure), and a discrete-trials schedule, in which rats were trained to discriminate the duration of light stimuli (interval bisection task). METHODS: In experiment 1, rats were trained under the free-operant psychophysical procedure to respond on two levers (A and B) in 50-s trials in which reinforcement was provided intermittently for responding on A during the first half and on B during the second half of the trial. For one group, repetitive switching between levers was permitted; for another group, it was prevented. In experiment 2, rats were exposed to press lever A after a 2-s stimulus and lever B after an 8-s stimulus, and were then tested with stimuli of intermediate duration. For one group, a 'poke response' (depression of a central tray flap) was required after stimulus presentation to effect lever presentation; for the other group, this requirement did not operate. In both experiments, quantitative indices of timing were derived from the psychophysical functions (%B responding vs time). RESULTS: In experiment 1, d-amphetamine increased the Weber fraction and displaced the psychophysical curve to the left in both versions of the schedule, as well as producing rate-dependent suppression of responding. In experiment 2, d-amphetamine increased the Weber fraction in both versions of the task without displacing the curve. CONCLUSIONS: These results confirm the disruptive effect of d-amphetamine on timing. The results of experiment 1 are consistent with the proposal that the drug reduces the period of the hypothetical pacemaker. However, the results of experiment 2 do not support this suggestion. Taken together, the results support the notion that different neural mechanisms may be involved in timing tasks involving temporal distribution of responding and discrimination of the duration of exteroceptive stimuli.

Analysis of Variance↗
PubMed2000

Comparison of the effects of clozapine, haloperidol, chlorpromazine and d-amphetamine on performance on a time-constrained progressive ratio schedule and on locomotor behaviour in the rat.

Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on "reinforcer efficacy". It has been proposed that the effects of neuroleptic drugs on operant behaviour are mediated by a reduction of "reinforcer efficacy". We examined the effects of two "conventional" neuroleptics (haloperidol and chlorpromazine) and an "atypical" neuroleptic (clozapine) on progressive ratio schedule performance; d-amphetamine was used as a comparison compound. In experiment 1, rats responded for a sucrose reinforcer on a time-constrained progressive ratio schedule (75-min sessions). After 66 preliminary training sessions, the rats received single doses (IP) of haloperidol (0.05, 0.1 mg kg(-1)). chlorpromazine (2, 4 mg kg(-1)), clozapine (0.5, 1, 2, 4, 8 mg kg(-1)), and d-amphetamine (0.2, 0.4, 0.8 mg kg(-1)), and the corresponding vehicle solutions. The highest ratio completed was reduced by haloperidol and chlorpromazine, and increased by clozapine. All three neuroleptics reduced the peak response rate, at least at the highest doses administered. Response rates on the lower and intermediate ratios could be described by a three-parameter equation proposed to account for fixed ratio schedule performance. Haloperidol reduced, and clozapine dose-dependently increased the "motivational" parameter (a); d-amphetamine reduced it at low doses and increased it at high doses. The three neuroleptics increased the "response time" parameter (delta). Un-reinforced locomotor behaviour, measured in experiment 2, was not significantly altered by haloperidol, chlorpromazine or clozapine, but was increased by d-amphetamine. These results are consistent with a reduction of reinforcer efficacy produced by haloperidol and an increase produced by clozapine; clozapine's effect is unlikely to reflect a general increase in locomotion. All three neuroleptics induced some degree of motor debilitation. The quantitative analysis of progressive ratio schedule performance may provide a useful adjunct to existing methods for separating effects of drugs on motivational and motor processes.

Animals↗
PubMed2000

Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules.

RATIONALE: Previous experiments have shown that the disruptive effect of central 5-HT depletion on interval timing behaviour is critically dependent upon the particular timing schedule used. However, it is not known how acute disruption of 5-HTergic function brought about by drugs acting at 5-HT receptors affects timing. OBJECTIVE: To examine the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two quantitative timing schedules, a free-operant schedule in which rats were trained to distribute their responses differentially between two levers during the course of a 50-s trial (free-operant psychophysical procedure) and a discrete-trials schedule in which rats were trained to discriminate the durations of light stimuli (interval bisection task). METHODS: In experiment 1, rats were trained under the free-operant psychophysical procedure to respond on two levers (A and B) in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half, of the trial. For one group, repetitive switching between levers was permitted; for another group, it was prevented. In experiment 2, rats were trained to press lever A after a 2-s stimulus and lever B after an 8-s stimulus, and were then tested with stimuli of intermediate durations. For one group, a 'poke response' (depression of a central tray flap) was required after stimulus presentation to effect lever presentation; for the other group this requirement did not operate. In both experiments, quantitative indices of timing were derived from the psychophysical functions (%B responding vs time). RESULTS: In experiment 1, 8-OH-DPAT (25, 50, 100 and 200 microg kg(-1) s.c.) displaced the psychophysical curve to the left in both versions of the schedule. In experiment 2, 8-OH-DPAT increased the Weber fraction in both versions of the task without displacing the curve. CONCLUSIONS: These results show that 8-OH-DPAT disrupts timing behaviour. The results of experiment 1 are consistent with the proposal that 5-HTergic mechanisms help to regulate the period of the hypothetical pacemaker. However, the results of experiment 2 do not support this suggestion. Taken together, the results support the notion that different neural mechanisms may be involved in timing tasks involving temporal distribution of responding and discrimination of the durations of exteroceptive stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Effects of central 5-hydroxytryptamine depletion on sensitivity to delayed and probabilistic reinforcement.

RATIONALE: The ascending 5-hydroxytryptaminergic (5-HTergic) pathways are believed to be involved in "impulse control". Rats whose 5-HTergic pathways have been destroyed are more liable than intact rats to select a smaller, immediate reinforcer rather than a larger, delayed reinforcer (impulsive choice), and recent evidence indicates that this effect of central 5-HT depletion reflects a change in the rate of time discounting (i.e. a change in the rate at which reinforcers become devalued as a function of delay). Delay of reinforcement and uncertainty of reinforcer delivery are believed to have equivalent effects on choice behaviour. However, it is not known whether central 5-HT depletion affects choice between probabilistic reinforcers. OBJECTIVE: We examined the effects of central 5-HT depletion on choice behaviour in two experiments: In experiment 1, rats chose between a smaller immediate reinforcer and a larger delayed reinforcer; in experiment 2, rats chose between a smaller certain reinforcer and a larger probabilistic reinforcer. METHODS: Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press two levers for food-pellet reinforcers in discrete-trials schedules. In free-choice trials, selection of lever A resulted in immediate delivery of one food pellet; selection of lever B resulted in delivery of 2 pellets, either following a delay (dB) (experiment 1) or with a probability (pB) less than 1 (experiment 2). RESULTS: In experiment 1, both groups showed declining choice of lever B (%B) as a function of dB. The lesioned group showed shorter indifference delays (D50: the value of dB corresponding to %B=50) than the sham-lesioned group. In experiment 2, both groups showed declining choice of lever B as a function of the odds against delivery of the two-pellet reinforcer, thetaB (thetaB=[1/pB]-1). There was no difference between the "indifference odds" (theta50: the value of thetaB corresponding to %B=50) between the two groups. In both experiments, the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. CONCLUSIONS: These results provide additional evidence that central 5-HTergic mechanisms are involved in time discounting, but provide no evidence for a similar role of 5-HT in rats' sensitivity to probabilistic reinforcement.

Animals↗
PubMed1999

Theory and method in the quantitative analysis of "impulsive choice" behaviour: implications for psychopharmacology.

Impulsive choice refers to the selection of small immediate gains in preference to larger delayed gains, or the selection of large delayed penalties in preference to smaller immediate penalties. Current theoretical interpretations of impulsive choice are reviewed, and a synthesis of these ideas, the "multiplicative hyperbolic model of choice", is presented. The model assumes that the value of a positive reinforcer increases as a hyperbolic function of its size, and decreases as a hyperbolic function of its delay and the odds against its occurrence. Each hyperbolic function contains a single discounting parameter which quantifies the organism's sensitivity to the variable in question. The hyperbolic discounting functions combine multiplicatively to determine the overall value of the reinforcer. Equivalent functions are postulated to govern the (negative) value of aversive events, the net value of an outcome reflecting the algebraic sum of the positive and negative values. The model gives rise to a quantitative methodology for studying impulsive choice, based on a family of linear indifference (null) equations, which describe performance under conditions of indifference, when the values of the reinforcers are assumed to be equal. This methodology may be used to identify individual differences in sensitivity to the magnitude, delay and probability of reinforcement. The methodology is also suitable for the quantitative evaluation of the effects of some pharmacological interventions on discounting parameters. Recent psychopharmacological studies of impulsive choice are reviewed, and the utility of indifference equations for extending this work, and developing a quantitative psychopharmacology of impulsive choice is discussed.

Animals↗
PubMed1999

Effect of central 5-hydroxytryptamine depletion on tolerance of delay of reinforcement: evidence from performance in a discrete-trials "time-left" procedure.

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance on a new discrete-trials version of the "time-left" procedure. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained in a discrete trials schedule in which reinforcers were provided for responding on either of two levers, A and B. At a random time point, t s after the start of each trial, the two levers were inserted into the operant chamber: a response on A resulted in the delivery of one food pellet after dA s, whereas a response on B resulted in the delivery of two pellets after 84-t s. The value of dA was varied between 1 and 12 s in different phases of the experiment. Both groups showed an increasing tendency to respond on lever B as a function of time within the trial. Logistic functions were fitted to the data from each group, and a value of the "indifference point" (T50: the time within the trial at which proportional choice of B attained a value of 50%) was derived for each rat. For each value of dA, the values of T50 were significantly greater in the lesioned rats than in the control rats, reflecting a rightward shift of the logistic function in the lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results provide further evidence for the involvement of the ascending 5HTergic pathways in the control of operant behaviour by delayed positive reinforcers.

5,7-Dihydroxytryptamine↗
PubMed1999

Effect of central 5-hydroxytryptamine depletion on performance in the free-operant psychophysical procedure: facilitation of switching, but no effect on temporal differentiation of responding.

This experiment examined the effect of destroying the ascending 5-hydroxytryptaminergic (5-HTergic) pathways on timing and switching behaviour in the free-operant psychophysical procedure. Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for sucrose reinforcement; sessions consisted of fifty 50-s trials in which reinforcers were available on a variable-interval 30-s schedule. In the first 25 s, of each trial, reinforcement was only available for responses on lever A; in the last 25 s, it was available only for responses on lever B. In phase 1 (70 sessions) repetitive switching between the levers was prevented by withdrawal of lever A after the first response on lever B in each trial; in phase 2 (40 sessions) this constraint on switching was removed; in phase 3 (40 sessions) the constraint was reinstated. Data were collected from probe trials (four per session) in which no reinforcers were delivered, during the last ten sessions of each phase. In all phases, both groups showed declining response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as percentage of overall response rate, could be described by a two-parameter logistic function. Removal of the constraint on switching reduced the slope of the function without changing the indifference point (time corresponding to 50% responding on lever B). The parameters of the timing function did not differ between the groups in any of the phases. However, the lesioned group showed a greater enhancement of switching rate during phase 2 than the control group. The levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results provide further evidence for the involvement of the ascending 5-HTergic pathways in switching between response alternatives, but cast doubt on our previous suggestion that the effects of 5-HT depletion on temporal differentiation of behaviour are mediated by facilitated switching.

5,7-Dihydroxytryptamine↗
PubMed1999

Effect of central 5-hydroxytryptamine depletion on changeover behaviour in concurrent schedules of reinforcement.

RATIONALE: Previous experiments have shown that rats whose 5-hydroxytryptaminergic (5-HTergic) pathways have been destroyed exhibit higher rates of switching between response alternatives on various temporal differentiation schedules. OBJECTIVE: This paper reports two experiments investigating the effect of central 5-HT depletion on switching between concurrent schedules of reinforcement which do not entail temporal differentiation of behaviour. METHODS: Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for sucrose reinforcement. In experiment 1, the rats were exposed to concurrent pairs of variable-time (VT) schedules specifying equal inter-reinforcement intervals; responses on a single "changeover lever" alternated between the two VT schedules. In experiment 2, the rats were exposed to concurrent pairs of variable-interval (VI) schedules specifying equal inter-reinforcement intervals; responses on one lever ("VI lever") earned reinforcers, while responses on the other lever ("changeover lever") alternated between the two VI schedules. RESULTS: In experiment 1, both groups showed longer "dwell-times" (intervals between successive changeover responses) when a reinforcer was delivered in the "dwell" than when no reinforcer was delivered ("win-stay" effect). The lesioned rats showed higher rates of changeover responding and shorter dwell-times (with and without reinforcer delivery) than the sham-lesioned group. In experiment 2, the rate of responding on the VI lever did not differ significantly between the two groups; however, the lesioned rats showed higher rates of changeover responding, shorter dwell-times (with and without reinforcer delivery) and smaller numbers of inter-changeover responses on the VI lever than the sham-lesioned group. In both experiments, the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. CONCLUSIONS: These results provide further evidence for the involvement of the ascending 5-HTergic pathways in behavioural "switching", and indicate that this is not restricted to temporal differentiation schedules.

Animals↗
PubMed1999

Interval timing performance in temporal lobe epilepsy: differences between patients with left and right hemisphere foci.

This experiment examined interval timing performance on a temporal reproduction procedure and a temporal discrimination (interval bisection) procedure in 19 patients with temporal lobe epilepsy (ten with a left-hemisphere focus [LTE group] and nine with a right- hemisphere focus [RTE group]), and 14 normal control subjects. In the temporal reproduction task, subjects were required to reproduce the durations of visual stimuli (0.5, 1, 2, 4, 8 s). In the temporal discrimination task, subjects were required to classify the visual stimuli as either 'short' or 'long'. Following exposure to the two standard durations (1 and 2 s), 'probe' trials were introduced in which the stimulus was presented for durations intermediate between the two standard durations. Psychophysical functions were derived from both timing tasks for each individual subject, as well as for the group mean data. The results showed that, compared to the normal subjects, the RTE group's timing ability was significantly compromized, as reflected by larger Weber fractions in both timing tasks. The LTE group's Weber fractions did not differ significantly from those of the control group; however they showed a leftward shift (i.e. a shorter bisection point) of the psychophysical function under the temporal discrimination task. The results suggest that the right and left hemispheres may play different roles in regulating interval timing performance.

Adult↗
PubMed1998

Effect of destruction of noradrenergic neurones with DSP4 on performance on a free-operant timing schedule.

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], on performance in a free-operant timing schedule. Rats received either systemic treatment with DSP4 or vehicle-alone injections. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reinforcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only for responses on lever B. Data were collected from probe trials (four per session), in which no reinforcers were delivered, during the last ten of 60 training sessions. Both groups showed decreasing response rates on lever A, and increasing response rates on lever B, as a function of time from the onset of the trial. Quantitative indices of timing behaviour were derived from a two-parameter logistic function fitted to the relative response rates on lever B (response rate on lever B, expressed as a percentage of overall response rate); this function accounted for > 90% of the data variance in each group. The DSP4-treated group showed a significantly lower value of the indifference point (i.e. the time corresponding to 50% responding on lever B) than the control group. The slope of the function and the rate of switching between response alternatives did not differ significantly between the two groups. The concentrations of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the concentrations of dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were not significantly altered. It is suggested that results may be consistent with a role of the dorsal ascending noradrenergic pathway in behavioural "arousal".

Animals↗
PubMed1998

5-hydroxytryptamine and impulse control: prospects for a behavioural analysis.

Impulsiveness is a significant clinical problem associated with a variety of psychiatric and neuropsychiatric disorders. Clinical and experimental studies have provided evidence that individuals displaying impulsive behaviour tend to show signs of deficient functioning of the ascending 5-hydroxytryptaminergic (5-HTergic) pathways of the brain. A persistent problem in investigations of the biological basis of impulsive behaviour has been the lack of a satisfactory definition of 'impulsiveness', as distinct from other behavioural features, such as aggression, which are often apparent in 'impulsive' individuals. Research in the experimental analysis of behaviour suggests that two important characteristics of 'impulsiveness' are (i) deficient tolerance of delay of gratification and (ii) inability to inhibit or delay voluntary behaviour; both of these characteristics are amenable to study in laboratory animals. We describe some delayed reinforcement and delayed response paradigms which purport to capture these behavioural characteristics, and review recent evidence that manipulation of 5-HTergic function alters behaviour in these paradigms. It is argued that the two characteristics of 'impulsiveness' are themselves the product of disturbance of more fundamental behavioural processes; the nature of these processes is considered.

Animals↗