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  • Serotonin  (4)
  • Antidepressant  (1)
  • 1
    ISSN: 1432-2072
    Schlagwort(e): Key words Impulsivity ; Amphetamine ; Antidepressant ; Haloperidol ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The effects of drugs on one aspect of impulsive behaviour were evaluated using a schedule in which rats were trained to complete a fixed consecutive number of responses on one of two levers before pressing the second to obtain a reinforcer (FCN). Terminating the chain before completing the FCN resulted in the omission of the food, and can be considered an impulsive decision. Two groups of food-deprived rats were trained to press either 8 or 32 times on the left lever (FCN lever) of a two lever operant chamber before pressing the right lever (Reinforcement lever) to deliver a food pellet. Responding on the Reinforcement lever before completion of the sequence resulted in a short time-out and the rat had to begin the sequence again. After responding had stabilised, the rats were treated with a range of doses of a number of drugs. Impulsivity was assessed by several measures, including the mean chain length and the proportion of chains terminating in food delivery, and the distribution of chain lengths was analysed. The efficiency of the rats was similar under both FCN 8 and FCN 32, although it was more difficult to maintain a consistent baseline under FCN 32. Under the FCN 8 schedule, significant decreases in chain length were obtained with d-amphetamine (0.8–2.4 mg/kg), haloperidol (0.1 mg/kg), ethanol (1 and 3 g/kg) and chlordiazepoxide (10.0 mg/kg), and there were alterations in other measures consistent with an increase in impulsivity. Imipramine (1–10 mg/kg), citalopram (1–10 mg/kg) and metergoline (0.3–3.0 mg/kg) had no effect on mean chain length, although the first two drugs shifted the chain length distribution to the left. d-Amphetamine (0.4–1.2 mg/kg) and PCPA (100 mg/kg) reduced chain length and had other effects consistent with increased impulsivity under FCN 32 schedule, whereas imipramine had little, and citalopram no, effect. Taken generally, effect of the active drugs was relatively non-specific, including both a reduction in response rate and alterations in choice measures proposed to reflect an increase in impulsivity. Detailed analysis of the effect of amphetamine revealed that three processes were at work: chain shortening, an increased preference for the lever most closely associated with food delivery, and a gradual shift in the control over responding from the response sequence (pattern) to the individual lever press (act).
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 102 (1990), S. 485-491 
    ISSN: 1432-2072
    Schlagwort(e): Locomotor activity ; Serotonin ; 8-OH-DPAT ; Mouse ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of 8-OH-DPAT on locomotor activity have not yet been clearly defined. Tricklebank et al. (1984) and Dourish et al. (1985) provide evidence that 8-OH-DPAT increases activity, whereas Mittman and Geyer (1989), Hillegaart et al. (1989) and Carli et al. (1989) suggest that it is reduced by the drug. In the present study, the effects of 8-OH-DPAT on locomotor activity and rearing were examined in habituated and unhabituated mice and rats. The effects of the drug were followed for up to 2 h in the mouse and up to 4 h in the rat. In unhabituated mice and rats, doses of 0.1 mg/kg or more of 8-OH-DPAT blocked activity during the period post-injection when control levels of activity were highest. However, after about 60 min in mice and 150 min in the rat a marked hyperactivity was observed, which was followed by a period of increased rearing. In habituated mice this biphasic effect on locomotor activity was also observed, but there was no increase in rearing. In habituated rats there was no decrease in locomotor activity, rather a biphasic increase was observed. The effects of 8-OH-DPAT on locomotor activity immediately post-injection are interpreted as being a result of the stereotyped, uncoordinated “ambulation” which forms a part of the 5-HT syndrome, and which results in a level of activity intermediate between that of unhabituated and habituated rats. The mechanism by which 8-OH-DPAT produces elevated locomotor activity and increased rearing seen 60 min or more post-injection is not yet known, but may be a result of brain concentrations of the drug falling to a low, but still effective level.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 146 (1999), S. 348-361 
    ISSN: 1432-2072
    Schlagwort(e): Key words Impulsivity ; Personality ; Serotonin ; Behaviour
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The concept of impulsivity covers a wide range of ”actions that are poorly conceived, prematurely expressed, unduly risky, or inappropriate to the situation and that often result in undesirable outcomes”. As such it plays an important role in normal behaviour, as well as, in a pathological form, in many kinds of mental illness such as mania, personality disorders, substance abuse disorders and attention deficit/hyperactivity disorder. Although evidence from psychological studies of human personality suggests that impulsivity may be made up of several independent factors, this has not made a major impact on biological studies of impulsivity. This may be because there is little unanimity as to which these factors are. The present review summarises evidence for varieties of impulsivity from several different areas of research: human psychology, psychiatry and animal behaviour. Recently, a series of psychopharmacological studies has been carried out by the present author and colleagues using methods proposed to measure selectively different aspects of impulsivity. The results of these studies suggest that several neurochemical mechanisms can influence impulsivity, and that impulsive behaviour has no unique neurobiological basis. Consideration of impulsivity as the result of several different, independent factors which interact to modulate behaviour may provide better insight into the pathology than current hypotheses based on serotonergic underactivity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-2072
    Schlagwort(e): Key words Ethanol ; Serotonin ; Delayed reinforcement ; Self-control ; Impulsivity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Tolerance to delay of reinforcement has been proposed as an important facet of self-control in both animals and man. Poor self-control, leading to impulsive behaviour, can be a major problem if it reaches pathological levels. Objectives: The effects of five serotonergic drugs were compared to those of ethanol on a procedure for measuring tolerance to delay of reinforcement in rats in order to elucidate further the role of the serotonin systems in the regulation of impulsive behaviour. Methods: Rats were trained to choose between a single food pellet (small reinforcer) delivered immediately or five food pellets (large reinforcer) delivered after programmed delays. At the start of each session, there was no delay between the response and delivery of the large reinforcer, but this was increased stepwise during the session to delays of 10, 20, 40 and 60 s. Results: The rats showed consistent preference for the larger reinforcer when it was not delayed but showed a shift in preference as the session continued, so that they preferred the small reinforcer when the large was delayed by 40 or 60 s. Ethanol at a dose of 1.0 g/kg produced a significance increase in preference for the small, immediate reinforcer throughout the session, although there were marked individual differences in the size of the effect. A similar, but somewhat smaller effect was seen with the 5-HT2 agonist, DOI, at a dose of 1.0 mg/kg. In contrast, the 5-HT1A agonist, 8-OH-DPAT (0.3 mg/kg) reduced preference for the large reinforcer at the start of the session, and reduced preference for the small reinforcer at the end of the session, i.e. produced a regression to indifference. Lower doses of these three drugs, and treatment with the 5-HT receptor subtype selective antagonists WAY-100635 (5-HT1A: 0.01–0.1 mg/kg), ritanserin (5-HT2: 0.1 and 0.3 mg/kg) and MDL-72222 (5-HT3: 1.0 and 3.0 mg/kg) had no significant effects on reinforcer choice. Conclusion: These data show that ethanol and DOI increase preference for the immediate reinforcer, which can be construed as evidence of an increase in impulsive behaviour (reduction in self control), whereas selective blockade of the 5-HT1A, 5-HT2 or 5-HT3 receptors using selective antagonists does not affect self-control.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-2072
    Schlagwort(e): Key words Reaction time ; Impulsivity ; Serotonin ; 8-OH-DPAT ; DOI
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: The serotonergic systems have been implicated in the pathological impulsive behaviour on the basis of both clinical and preclinical data. However, impulsivity is probably made up of several independent factors, and the involvement of the diverse regulatory mechanisms of the serotonergic systems has not been widely studied. Objective: The influence of a range of serotonergic agents on impulsivity was examined using a procedure designed to test the dimension of impulsivity termed ”reflection-impulsivity” in rats. Methods: An operant procedure was used in which the need to wait before responding was made explicit by using a signal which increased in predictive value the longer the subject waited before responding. First, the rats learned that a light signal indicated the availability of a food reinforcer if one of two levers was pressed. In the test procedure, on each trial, when the light was turned on it was only 50% likely to indicate the ”correct” lever. After a brief interval it was turned off and on again, this time with a slightly higher probability (〉50%) of indicating the correct lever. Over a period of a few seconds the probability that the light indicated the correct lever increased to almost 100%. Thus a quick response to the light would result in many errors, whereas a slow response could always result in food delivery. Once trained the rats were treated with a series of drugs: citalopram, (selective serotonin reuptake inhibitor), p-chloramphetamine (PCA, serotonin releaser), 8-OH-DPAT (5-HT1A agonist), RU24969 (primarily a 5-HT1B receptor agonist), DOI, (5-HT2 agonist), WAY-100,635 (5-HT1A antagonist), ritanserin (5-HT2 antagonist), and MDL-72222, (5-HT3 antagonist). Results: Of the test compounds, PCA, DOI and 8-OH-DPAT increased reaction times, whereas ritanserin reduced them. Citalopram and WAY-100,635 had no significant effects, RU-24969 appeared to disrupt responding, and MDL-72222 reduced premature responses and the number of short reaction times. Conclusions: Since agonists at the 5-HT1A and 5-HT2 receptors both reduced impulsivity in this procedure, these data suggest that serotonin may promote ”reflection” in this procedure via stimulation of these receptor subtypes.
    Materialart: Digitale Medien
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