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Biomedical subjects

E Szabadi

Publications and source records attributed to E Szabadi.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

Interaction between antidepressants and d-amphetamine on variable-interval performance.

Four experiments were carried out investigating the interactions between some antidepressant drugs (imipramine, desipramine, fluvoxamine, trazodone (4 and 8 mg/kg) and d-amphetamine (0.1-3.2 mg/kg) on operant behaviour maintained under a variable-interval 80-s schedule of sucrose reinforcement; each experiment employed 12 rats. d-Amphetamine exerted a dose-related suppressant effect on response rate. Imipramine and desipramine given alone had no effect on response rate, whereas fluvoxamine (both doses) and the higher dose of trazodone produced significant increases in response rate. Pretreatment with imipramine, desipiramine or fluvoxamine significantly potentiated the suppressant effect of d-amphetamine on responding; pretreatment with trazodone had no significant effect. The potentiating effect of imipramine and desipramine may be related to their well known uptake blocking actions. The fact that fluvoxamine, a selective inhibitor of 5-hydroxytryptamine (5HT) uptake, also potentiated the effect of d-amphetamine suggests that the suppressant effect of d-amphetamine on operant behaviour may involve 5HT as well as catecholamine release. The lack of effect of trazodone may reflect its failure to influence uptake mechanisms. On the basis of a formal model couched in terms of Herrnstein's (1970) equation, it is suggested that imipramine, desipramine and fluvoxamine may have enhanced d-amphetamine's ability to reduce response capacity; it is suggested that the data do not provide evidence for an interaction between the antidepressants and the putative "motivation-enhancing" effect of d-amphetamine.

Animals

The action of microelectrophoretically applied (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI) on single cortical neurones.

1. The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane. 2. DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses. 3. In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine. 4. The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected. 5. The alpha-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected. 6. It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by alpha-adrenoceptors.

Animals