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  • 1
    ISSN: 1432-2072
    Schlagwort(e): Animal model ; Catalepsy ; Neuroleptics ; Paw test ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) and atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 72 (1988), S. 299-304 
    ISSN: 1432-1106
    Schlagwort(e): EMG ; Forelimb muscle ; Hindlimb muscle ; Neostriatum ; Nucleus accumbens
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The present set of experiments were performed to evaluate the role of the nucleus accumbens in the regulation of forelimb muscle tone. Rats were chronically implanted with cannulae aimed at the nucleus accumbens or the neostriatum and with EMG electrodes in the triceps or the gastrocnemius soleus muscle. The experiments were all performed in non-anaesthetised freely moving animals. The results show that haloperidol induced an increase in triceps muscle tone when injected into the nucleus accumbens but not when injected into the neostriatum. Likewise it was found that haloperidol induced an increase in gastrocnemius soleus muscle tone when injected into the neostriatum but not when injected into the nucleus accumbens. The increase in triceps muscle tone seen after intra-accumbens haloperidol was only briefly attenuated by apomorphine, whereas phenylephrine produced a more long lasting antagonism. The present data show that in addition to the cortex, subcortical structures also appear to possess a certain topography, with forelimb rigidity being mediated, at least in part, by the nucleus accumbens, and hindlimb rigidity, at least in part by the neostriatum. In addition it appears that the effects of haloperidol in the nucleus accumbens on triceps muscle tone are primarily mediated by α1 adrenergic receptors, although a minor role of dopamine D2 receptors cannot be fully excluded.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-2072
    Schlagwort(e): Key words Amphetamine ; Animal model ; Conditioned taste aversion ; Dopamine ; Latent inhibition ; Neostriatum ; Nucleus accumbens ; Schizophrenia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Repeatedly presenting a non-reinforced stimulus normally retards conditioning to this stimulus when it is coupled to a reinforcer. This phenomenon is called latent inhibition. Since latent inhibition is disturbed after systemic administration of amphetamine, the present study investigated the role of the mesolimbic and nigrostriatal dopamine terminal fields in latent inhibition using a conditioned taste aversion (CTA) paradigm. In this paradigm, a 5% sucrose solution was used as the test stimulus and lithium chloride (LiCl) as the CTA inducing drug. The degree of CTA was assessed by measuring the sucrose preference in a two-bottle sucrose/water choice paradigm 24 h after the LiCl injection. Since conditioned taste aversion has so far not been used to evaluate the role of dopamine in latent inhibition, we first studied the effects of systemic application of amphetamine. The results show that intraperitoneal injections of 0.25 or 0.5 mg/kg d-amphetamine sulphate (given at preexposure and conditioning) significantly disrupted latent inhibition, by selectively reducing sucrose preference in the preexposed group. This could not be attributed to a reduced sucrose intake during preexposure or to a conditioned taste aversion effect of amphetamine itself. In experiment 2 local bilateral administration of 10 μg/0.5 μl amphetamine into the nucleus accumbens or the dorsal striatum was given in the pre-exposed and the conditioning phase, after which the rats were allowed to drink for a fixed period of time. The results show a significant reduction in latent inhibition after intrastriatal, but not after intra-accumbens injections of amphetamine. Intra-accumbens injections of amphetamine, however, significantly reduced fluid intake during preexposure and conditioning. In experiment 3, we therefore repeated this experiment, but allowed the animals to drink only a restricted amount of liquid during preexposure and conditioning. Again the results show a disruption of latent inhibition after intrastriatal, but not intra-accumbens injections of amphetamine. These experiments emphasize the importance of the nigrostriatal dopamine system in the disruption of latent inhibition, at least when using the conditioned taste aversion paradigm. A possible mechanism by which the dorsal striatum might influence latent inhibition is discussed.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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