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  • 1
    Electronic Resource
    Electronic Resource
    Effects of 6-hydroxydopamine lesions of locus coeruleus on startle in rats (1981)
    Springer
    Psychopharmacology 73 (1981), S. 394-398 
    Details
    ISSN: 1432-2072
    Keywords: Locus coeruleus ; Startle ; Habituation ; Sensitization ; Lesions ; Norepinephrine ; 6-Hydroxydopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine the possible involvement of the norepinephrine (NE) containing neurons of the locus coeruleus in the modulation of behavioral reactivity to sensory stimulation, bilateral chemical lesions of the locus coeruleus were made by local injection of the catecholamine neurotoxin 6-hydroxydopamine. Both histochemical and biochemical analyses confirmed the effectiveness of the lesions in specifically eliminating the NE containing cell bodies of the locus coeruleus and reducing the NE content of the hippocampus and substantia nigra by 45% and 69% respectively. Rats were tested both 5 and 36 days after lesioning for their startle response to a repetitive series of tactile stimuli. On both days, locus coeruleus lesioned rats exhibited consistently reduced startle responses throughout the stimulus series. Additionally, lesioned rats showed a far more rapid rate of response habituation, particularly in the first test. The results are discussed in terms of a possible influence of the locus coeruleus on the process of sensitization to sensory stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426474
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  • 2
    Electronic Resource
    Electronic Resource
    Sequential changes in behavior induced by continuous infusions of amphetamine in rats (1987)
    Springer
    Psychopharmacology 91 (1987), S. 217-220 
    Details
    ISSN: 1432-2072
    Keywords: Rats ; Continuous amphetamine ; Locomotor activity ; Startle ; Stereotypy ; Amphetamine psychosis ; Dopamine ; Holeboard ; Animal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats infused with amphetamine (0.65 mg/kg/h) for 5 days through Alzet (Tm) minipumps displayed a multiphasic sequence of behavioral changes. The behavior of the animals was characterized during daily 40-min test sessions in behavioral pattern monitors (BPM). Within 24 h after implantation of the minipumps, rats infused with amphetamine exhibited prolonged periods of oral stereotypies (licking or biting). By the 3rd day this stereotypy was replaced with locomotor and investigatory activation as the predominant response pattern. In addition, the magnitudes of tactile startle responses were reduced in a separate group of animals infused with amphetamine for 9 days. In accord with previous findings, dopamine (DA) in the corpus striatum was markedly reduced by the 3rd day, whereas DA in the nucleus accumbens was transiently increased. These results indicate that continuous infusion of amphetamine produces a relatively selective depletion of striatal DA resulting in a reduction in amphetamine-induced stereotypy with a corresponding increase in locomotor activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217066
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Dopaminergic stimulation disrupts sensorimotor gating in the rat (1988)
    Springer
    Psychopharmacology 94 (1988), S. 507-514 
    Details
    ISSN: 1432-2072
    Keywords: Apomorphine ; Amphetamine ; Haloperidol ; Dopamine ; Startle ; Sensory gating ; Prepulse inhibition ; Schizophrenia ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition is a cross-species phenomenon in which reflex responses to discrete sensory events are modified by weak prestimulation. In experiments designed to investigate the neuropharmacological mechanism of this form of information processing, and its relevance to schizophrenic psychopathology, apomorphine (0.125–4.0 mg/kg) and d-amphetamine (0.5–4.0 mg/kg) were administered to rats in an attempt to modify prepulse inhibition of the acoustic startle response. Rats were presented with 40 ms, 118 dB[A] acoustic pulses which were intermittently preceded by a weak 80 dB[A] acoustic prepulse. Both apomorphine and d-amphetamine induced a significant loss of prepulse inhibition, as reflected by increased pulse-preceded-by-prepulse versus pulse-alone startle magnitudes. Haloperidol (0.1 mg/kg), a specific D2 dopamine receptor antagonist, prevented the effects of 2.0 mg/kg apomorphine on prepulse inhibition, while having little effect by itself. An additional study investigated the effects of chronic intermittent administration of 2.5 mg/kg d-amphetamine. Rats given amphetamine for 8 consecutive days also displayed a loss of prepulse inhibition, with no evidence of tolerance. Finally, prepulse inhibition was examined under high- and low-intensity startle stimulus conditions; apomorphine (1.0 mg/kg) induced a loss of prepulse inhibition under both intensity conditions in approximately equal proportion. The results of these studies suggest a connection between sensorimotor gating, as measured by prepulse inhibition, and dopaminergic overactivity, supporting suggestions that information processing deficits in schizophrenia may be responsible for some psychotic symptoms and their effective treatment by antipsychotic D2 dopamine antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212846
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  • 4
    Electronic Resource
    Electronic Resource
    8-OH-DPAT disruption of prepulse inhibition in rats: reversal with (+)WAY 100,135 and localization of site of action (1995)
    Springer
    Psychopharmacology 117 (1995), S. 41-48 
    Details
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT 8(-hydroxy-2(di-n-propylamino)tetralin ; (+)WAY 100,135 ; 5-HT1A ; Median raphe Dorsal raphe ; Prepulse inhibition ; Startle ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies have implicated central serotonergic systems in the modulation of prepulse inhibition (PPI), an operational measure of sensorimotor gating, which has been used to identify gating deficits in psychiatric disorders, such as schizophrenia, Huntington's disease, and obsessive compulsive disorder. Both serotonin (5-HT) releasers and agonists at 5-HT1A, 5-HT1B, and 5-HT2 receptors reduce PPI in the rat. The present experiments demonstrate that the disruption of PPI in rats induced by the systemic administration of the 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2(di-n-propylamino)tetralin; 0.2 mg/kg), can be attenuated by the novel, selective 5-HT1A antagonist (+)WAY 100,135, (20.0 mg/kg),N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenyl-propanamide. Further experiments addressing the central site of action of 8-OH-DPAT revealed that the microinjection of 8-OH-DPAT (5.0 µg/0.5 μl) into either the median raphe nucleus (MR) or dorsal raphe nucleus (DR) disrupts PPI. The reduction in PPI produced by intra-raphe microinjections of 8-OH-DPAT was prevented by a systemic injection of (+)WAY 100,135. These results support the hypothesis that somatodendritic 5-HT1A autoreceptors within the midbrain raphe subserve the PPI-disruptive effects of systemically administered 8-OH-DPAT. The decrement in PPI after intra-raphe infusions of a high dose of 8-OH-DPAT, however, was substantially less than the decrement in PPI after systemic administration of the drug. Hence, sites in addition to the somatodendritic autoreceptors may also play an important role in 8-OH-DPAT-induced disruption of PPI. Together with previous reports that 5-HT releasers and other 5-HT agonists also disrupt PPI, the results support the hypothesis that the serotonergic system modulates PPI through multiple receptor and anatomical systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245096
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  • 5
    Electronic Resource
    Electronic Resource
    Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine (1995)
    Springer
    Psychopharmacology 122 (1995), S. 198-201 
    Details
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Clozapine ; Startle ; Sensorimotor gating ; NMDA ; Dizocilpine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246096
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  • 6
    Electronic Resource
    Electronic Resource
    Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition (1998)
    Springer
    Psychopharmacology 135 (1998), S. 194-200 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prepulse inhibition ; Startle ; Clozapine ; Schizophrenia ; Dopamine D4 receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent evidence suggests that the dopamine D4 receptor may play a role in schizophrenia, and that the atypical properties of the antipsychotic clozapine may be attributable in part to its antagonistic actions at this receptor. In the present study, clozapine and three other compounds having D4 dopamine receptor antagonist properties were examined for their effectiveness in reducing losses in prepulse inhibition (PPI) induced in rats by the dopamine receptor agonist apomorphine. Previously, activity in the PPI model has been shown to correlate highly with the antipsychotic potency of a number of neuroleptics. As previously reported, clozapine (1–5.6 mg/kg) significantly reduced apomorphine-induced PPI deficits. The three D4-selective compounds, CP-293,019 (5.6–17.8 mg/kg), U-101,387 (3–30 mg/kg) and L-745,870 (1–10 mg/kg), also significantly blocked the losses in PPI produced by apomorphine. Taken together, these results suggest that dopamine receptor antagonists with selectivity for the D4 dopamine receptor subtype may be effective in the treatment of schizophrenia, while being less likely to produce dyskinesias associated with D2 receptor antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050501
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  • 7
    Electronic Resource
    Electronic Resource
    Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats (1990)
    Springer
    Psychopharmacology 102 (1990), S. 1-4 
    Details
    ISSN: 1432-2072
    Keywords: Apomorphine ; Startle ; Prepulse inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Separate experiments conducted in two different laboratories assessed the importance of the prepulse intensity in the ability of apomorphine to reduce prepulse inhibition of acoustic startle responses. Rats were presented with noise bursts alone or noise bursts 100 ms after presentation of prepulse stimuli ranging from 70 to 85 or 90 dB. Throughout testing, the background noise was maintained at 65 dB. In both laboratories, apomorphine markedly decreased the absolute magnitude of prepulse inhibition when the prepulse stimuli were no more than 10 dB above the background. With more intense prepulse stimuli, apomorphine had no significant effect on prepulse inhibition. Hence, apomorphine does not interfere with the inhibitory process which actually mediates prepulse inhibition, but appears to affect the detectability of the prepulse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245735
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of sustained cocaine exposure on sensorimotor gating of startle in rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 253-260 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Neurotoxicity ; Prepulse inhibition ; Schizophrenia ; Startle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Deficient sensorimotor gating, as measured by a relative loss of prepulse inhibition (PPI) of the startle reflex, has been reported in schizophrenia patients and in rats treated acutely with dopamine (DA) agonists or other psychotomimetic agents. For this reason, PPI has been used as a cross-species measure for studying the neurochemistry of specific information processing deficits in schizophrenia. Cocaine is a DA reuptake inhibitor which can precipitate psychosis after sustained use in humans. In rats, sustained exposure to cocaine results in neuropathological and neurochemical changes in several brain regions, and is also associated with specific prolonged behavioral abnormalities. In the present study, we examined the effects of both acute and sustained cocaine administration on PPI and other measures of the startle reflex in rats. Cocaine produced a significant, dose-dependent reduction in PPI, both after acute administration, and after 3 days of sustained administration via implanted subcutaneous pellets. PPI returned to control levels when rats were tested 10 days after sustained (5 day) cocaine administration. The effects of acute cocaine administration on PPI are consistent with those of other DA agonists and psychotomimetics, but PPI does not appear to be sensitive to lasting effects of a method of prolonged cocaine administration associated with neuropathological and neurochemical changes in several brain regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050887
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