Biomedical subjects

C M Bradshaw

Publications and source records attributed to C M Bradshaw.

At least 19 recordsLinked to original sources

PubMed1995

Retarded acquisition of a temporal discrimination following destruction of noradrenergic neurones by systemic treatment with DSP4.

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (> 90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, 'probe' trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.

Adrenergic Agents↗

PubMed1995

The role of the ascending 5-hydroxytryptaminergic pathways in timing behaviour: further observations with the interval bisection task.

This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on rats' ability to discriminate between two durations. Rats received injections of 5,7-dihydroxytryptamine into the median and dorsal raphe nuclei or sham lesions. They were trained to press lever A following a 2-s presentation of a light and lever B following an 8-s presentation of the light. For some rats, the levers were inserted into the chamber immediately after stimulus presentation ("no-poke-requirement"); for others, the levers were not inserted until a flap covering the food tray positioned midway between the levers had been depressed ("poke-requirement"). When stable performance was attained, "probe" trials were introduced in which the light was presented for intermediate durations. Logistic functions were derived relating percent choice of lever B to log stimulus duration. Under the "no-poke-requirement" condition, the bisection point (duration yielding 50% choice of lever B) was shorter in the lesioned rats than in the control rats. Under the "poke-requirement" condition, this effect of the lesion was attenuated. There was no effect of the lesion on the Weber fraction under either condition. 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 altered. It is proposed that rats may attain accurate timing under the interval bisection task by moving from one lever to the other during stimulus presentation; this movement may be facilitated by destruction of the 5HTergic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1995

Effects of reboxetine and desipramine on the kinetics of the pupillary light reflex.

1. The aim of the study was to examine the effects of single doses of two antidepressants (desipramine and reboxetine) on three kinetic parameters (latency, amplitude, 75% recovery time) of the pupillary light reflex response. 2. Six healthy male volunteers participated in three experimental sessions at biweekly intervals. Each session was associated with one of three treatment conditions (placebo, desipramine 100 mg, reboxetine 4 mg). Subjects were allocated to sessions and treatments double-blind according to a Latin Square design. 3. Pupil diameter was measured in the dark with binocular television pupillometry. Reflex responses were evoked by 12 light stimuli (5.3 x 10(-5)-3.5 mW cm-2; 500 ms), and the kinetic parameters of each response were recorded. 4. The amplitude and 75% recovery time were positively, and latency was negatively correlated with the logarithm of light stimulus intensity. In the presence of the antidepressants the latency was prolonged, the amplitude was reduced and the 75% recovery time was shortened. There was a positive linear relationship between reflex amplitude and recovery time under all three treatment conditions; this relationship was not significantly affected by the antidepressants. 5. The effects of the antidepressants on latency and amplitude are consistent with the blockade of muscarinic cholinoceptors in the iris, whereas the shortening of the recovery time appears to be secondary to the reduction in amplitude.

Administration, Oral↗

PubMed1994

Facilitated acquisition of a temporal discrimination following destruction of the ascending 5-hydroxytryptaminergic pathways.

This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition and performance of discrimination between two brief time intervals. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats were trained in a series of discrete trials to press lever A following a 200-ms presentation of a light stimulus and lever B following an 800-ms presentation of the same stimulus. Both groups gradually acquired accurate performance, attaining 80%-85% accuracy by the end of 40 sessions. The lesioned group learnt the task significantly faster than the control group. When stable performance had been attained, "probe" trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) did not differ significantly between the two groups; however, the Weber fraction was significantly smaller in the lesioned group than in the control group. The levels of 5HT and 5-hydroxy-indole-acetic acid were markedly reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results indicate that destruction of the 5HTergic pathways facilitates acquisition of a temporal discrimination. The lack of an effect of the lesion on the bisection point contrasts with our previous finding using longer stimulus durations; it is suggested that different behavioural processes may underlie millisecond-range and second-range temporal discrimination, and that these may be differently affected by 5HT depletion.

5,7-Dihydroxytryptamine↗

PubMed1994

Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with the fixed-interval peak procedure.

Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader "spread" of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.

5,7-Dihydroxytryptamine↗

PubMed1994

Detection of acquired deficits in general intelligence using the National Adult Reading Test and Raven's Standard Progressive Matrices.

A multiple regression equation for estimating premorbid Raven's Standard Progressive Matrices (RSPM) scores on the basis of age and the National Adult Reading Test (NART) was derived. A sample of patients with confirmed cerebral lesions was examined to determine the proportion of patients with significant discrepancies between their predicted and obtained RSPM performance. The sensitivity of the procedure was modest (52 per cent), although a comparison with discrepancies between premorbid and current performance on the Wechsler scales indicated that the RSPM was more sensitive to neuropathology. These findings suggest that when NART-intelligence test comparisons are used to diagnose cerebral impairment, the likelihood of a false-negative diagnosis is high.

Adult↗

PubMed1993

Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on choice between delayed reinforcers.

The possible involvement of the ascending 5-hydroxytryptaminergic (5HTergic) pathways in determining the effectiveness of delayed positive reinforcers was investigated using Mazur's (1984) adjusting-delay paradigm. Fourteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats made repeated choices in a two-lever operant conditioning chamber between a smaller reinforcer delivered after a 2-s delay and a larger reinforcer delivered after a variable delay, the length of which was determined by the subject's previous choices. When the two reinforcers consisted of one and two food pellets, the "indifference point" (the delay to the larger reinforcer that rendered the two reinforcers equally effective) was shorter in the lesioned group than in the control group. Increasing the sizes of the reinforcers to three and six pellets reduced the indifference point in both groups and abolished the between-group difference. The levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were greatly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected. The results are consistent with the suggestion that the 5HTergic pathways play a role in maintaining the effectiveness of delayed reinforcers.

5,7-Dihydroxytryptamine↗

PubMed1993

Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with an interval bisection task.

Seventeen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei: 12 rats received sham injections. The rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and to press lever B following an 8-s presentation of the same stimulus. Both groups learnt the task rapidly and maintained > 90% accuracy throughout the experiment. When stable performance had been attained, "probe" trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) was significantly shorter in the lesioned group than in the control group. There was no significant difference between the slopes of the psychophysical functions or the Weber fractions derived for the two groups. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour, but suggest that destruction of these pathways does not disrupt the capacity for temporal discrimination.

5,7-Dihydroxytryptamine↗

PubMed1993

Does the effect of central 5-hydroxytryptamine depletion on timing depend on motivational change?

In a previous experiment we found that destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways by microinjection of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei resulted in impaired acquisition of temporal differentiation under an interresponse-time-greater-than-15-s (IRT > 15 s) schedule of sucrose reinforcement. This paper reports three experiments, the results of which bear on the interpretation of that finding. In Experiment 1, 32 rats were trained for 120 sessions under the IRT > 15 s schedule; then 16 received lesions of the 5HTergic pathways and 16 received sham lesions. Comparisons of the IRT frequency distributions of the two groups showed that the lesion produced a significant reduction of the mean IRT and an increase in the dispersion of IRTs, as expressed by the coefficient of variation. Obtained reinforcement rates were significantly reduced in the lesioned group, but response rates were not significantly altered. Levels of 5HT and 5-hydroxyindoleacetic acid were markedly reduced in all forebrain areas examined, without significant change in noradrenaline and dopamine levels. The results indicate that destruction of the 5HTergic pathways disrupts performance as well as acquisition of temporal differentiation. Experiments 2 and 3 examined whether changes in deprivation level and reinforcer magnitude, which are known to affect reinforcer value, would influence temporal differentiation in a similar fashion to destruction of the 5HTergic pathways. In experiment 2, 20 rats were trained under the IRT > 15 s schedule while maintained at 80% or 90% of free-feeding body weight; the more severe deprivation condition was associated with a longer mean IRT and a lower coefficient of variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Utility of the Modified Wisconsin Card Sorting Test in neuropsychological assessment.

Nelson's (1976) Modified Wisconsin Card Sorting Test (MCST) was evaluated and the utility of the conventional criterion and new threshold scores for identifying patients with frontal lobe disorder assessed. Measures of perseveration and other indices of performance on the MCST were not found to discriminate between patients with frontal and non-frontal lobe lesions, using either the conventional criterion or new threshold scores. In addition there were no significant differences between left- and right-sided lesioned patients. However, the task was found to have high specificity (98.7 per cent) and good sensitivity (45.6 per cent) to lesions irrespective of site indicating that it may be a useful screening test. The present findings are consistent with recent research with the original Wisconsin Test, that suggests that card-sorting performance may not be as differentially sensitive to frontal lobe disorder as has been thought hitherto.

Adult↗

PubMed1992

A comparison of the effects of fluvoxamine and amitriptyline on autonomic functions in healthy volunteers.

We have compared the effects of single oral doses of fluvoxamine (50 mg and 100 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced, double-blind, crossover design. Amitriptyline significantly reduced salivation, the miosis evoked by locally applied pilocarpine, and the sweat secretion evoked by locally applied carbachol. Fluvoxamine also significantly attenuated carbachol-evoked sweat gland activity, although to a smaller degree than amitriptyline; fluvoxamine did not significantly alter salivation or pilocarpine-evoked miosis. Neither treatment significantly altered the miotic responses evoked by brief light stimuli. Heart rate and blood pressure were not greatly affected by either treatment, although the fall in heart rate (erect posture) with placebo was significantly reduced by amitriptyline (100 mg). The results suggest that fluvoxamine has some anti-muscarinic activity in man, but is considerably less potent in this respect than amitriptyline.

Administration, Oral↗

PubMed1992

Impaired acquisition of temporal differentiation performance following lesions of the ascending 5-hydroxytryptaminergic pathways.

Nineteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 16 rats received sham injections. The rats underwent 50 daily training sessions under an interresponse-time-greater-than-15-seconds (IRT greater than 15 s) schedule of sucrose reinforcement. The lesioned group showed impaired acquisition of temporal differentiation, in that their response rates remained significantly higher and their obtained reinforcement frequencies significantly lower than those of the control (sham-lesioned) group. Comparison of the IRT frequency distributions obtained from the two groups during the last 5 days of training showed that the lesioned group produced a significantly higher proportion of very short IRTs (less than 3 s) than the control group; when these short IRTs were disregarded, the lesioned group displayed a significantly lower mean IRT and a significantly higher coefficient of variation than the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results suggest that destruction of the ascending 5HTergic pathways may reduce animals' capacity to inhibit positively reinforced operant behaviour, and may impair temporal discrimination.

5,7-Dihydroxytryptamine↗

PubMed1992

Choice between delayed reinforcers in a discrete-trials schedule: the effect of deprivation level.

Choice between two reinforcers differing in magnitude and delay was investigated in rats using a discrete-trials schedule in which the two reinforcers were associated with two levers (A and B); in each session 5 free-choice trials (A and B both available) were interspersed among 44 forced-choice trials (A alone, 22 trials; B alone, 22 trials). In Experiment 1, preference for the more concentrated of two sucrose solutions declined as the delay to that reinforcer was progressively increased. In Experiment 2, progressively increasing the delay to both reinforcers by the same amount resulted in a shift in preference away from the less concentrated solution. In Experiment 3, it was found that the decline in preference for the more concentrated solution as a function of the delay to that reinforcer was steeper when the rats were maintained at 90% than when they were maintained at 80% of their free-feeding body weights. This effect of deprivation level on choice is inconsistent with some current models of "self-control".

Animals↗

PubMed1992

Effect of high ambient temperature on the kinetics of the pupillary light reflex in healthy volunteers.

Miotic responses to brief light stimuli were studied in healthy volunteers under two ambient temperature conditions, 22 degrees C and 40 degrees C. The latency and amplitude of the light reflex did not differ between the two conditions, but the recovery time of the reflex was significantly shorter under the 40 degrees C condition than under the 22 degrees C condition. The results are consistent with the hypothesis that exposure to high ambient temperature results in an increased sympathetic drive to the iris dilator muscle but does not influence the parasympathetic light reflex.

Adult↗

PubMed1992

Choice between delayed reinforcers in an adjusting-delay schedule: the effects of absolute reinforcer size and deprivation level.

Choice between two reinforcers differing in magnitude and delay was investigated in rats using an adjusting-delay discrete-trials schedule in which the two reinforcers were associated with two levers (A and B). The delay to Reinforcer A (the smaller reinforcer) was always 2 sec, whereas the delay to Reinforcer B was varied in accordance with the distribution of choices in successive blocks of trials. In Experiment 1, the mean delay to the large reinforcer during the last 5 of 60 training sessions was greater when the rats were maintained at 80% than when they were maintained at 90% of their free-feeding body weights. In Experiment 2, the delay to the larger reinforcer was greater when the two reinforcers consisted of one and two 45-mg food pellets than when they consisted of three and six pellets. The results are consistent with a model of "self-control" which posits hyperbolic relations between reinforcer value and reinforcer magnitude, and between reinforcer value and delay of reinforcement.

Animals↗

PubMed1991

Evidence for an involvement of 5-hydroxytryptaminergic neurones in the maintenance of operant behaviour by positive reinforcement.

The possible involvement of the ascending 5-hydroxytryptaminergic (5HTergic) pathways in the maintenance of operant behaviour by positive reinforcement was examined using a quantitative paradigm based on Herrnstein's (1970) equation which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Nine rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham injections. The rats were trained to steady-state in a series of variable-interval schedules of sucrose reinforcement affording a range of reinforcement frequencies. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The value of KH (the parameter expressing the reinforcement frequency needed to obtain the half-maximum response rate) was significantly lower in the lesioned group than in the control group; the values of Rmax (the parameter expressing the maximum response rate) did not differ significantly between the two groups. The levels of 5HT and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, nucleus accumbens and hypothalamus were markedly reduced in all four regions in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected. The results indicate that damage to the central 5HTergic pathways resulted in an increase in the "value" of the sucrose reinforcer, without affecting the animals' response capacity. The results are consistent with the suggestion that the 5HTergic pathways may exert some limiting control on the "values" of certain reinforcers.

5,7-Dihydroxytryptamine↗

PubMed1991

Effects of clonidine and yohimbine on the pupillary light reflex and carbachol-evoked sweating in healthy volunteers.

The effects of single doses of clonidine hydrochloride (200 micrograms), yohimbine hydrochloride (22 mg), a combination of the two treatments, and placebo, on some autonomic functions were studied in healthy volunteers using a double-blind crossover design. Clonidine prolonged the recovery time of the light reflex, lowered systolic blood pressure and reduced subjectively rated alertness; these effects were reversed by yohimbine. Responsiveness of sweat glands to carbachol was not affected by the treatments.

Adult↗

PubMed1991

Relative and absolute reinforcement frequency as determinants of choice in concurrent variable interval schedules.

Rats were trained under concurrent schedules consisting of two equal variable interval component schedules providing sucrose solutions of different concentrations (0.6 M, 0.2 M; 50 microliters in each case) as the reinforcers. The mean interreinforcement interval specified by the schedules was varied from 10 to 640 sec. Absolute response rate in each component was an increasing hyperbolic function of reinforcement frequency. Relative response rate and relative time allocation revealed a consistent preference for the more concentrated solution; neither measure of preference was systematically related to reinforcement frequency. The results are consistent with Baum and Rachlin's (1969) extension of the matching law, and with a derivation of the matching law from the hyperbolic relation between absolute response rate and reinforcement frequency in variable interval schedules (Herrnstein, 1970).

Animals↗