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  • 1
    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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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Parametric determinants in pre-stimulus modification of acoustic startle: interaction with ketamine (1991)
    Springer
    Psychopharmacology 105 (1991), S. 162-168 
    Details
    ISSN: 1432-2072
    Keywords: Prepulse inhibition ; Ketamine ; Rat ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition of the acoustic startle response is a form of reflex modification known to be sensitive to drugs and to subtle procedural manipulations. The present study examined the importance of prepulse length and prepulse-pulse interval in the expression of prepulse inhibition and its modification by the noncompetitive N-methyl-d-aspartate antagonist, ketamine. In contrast to a previous report, ketamine disrupted prepulse inhibition at doses of 5.6 and 10 mg/kg when its short time course was taken into consideration. In a second experiment, the amount of prepulse inhibition was found to be directly related to prepulse length, with prepulse inhibition produced by shorter prepulse durations slightly more sensitive to disruption by ketamine. A third experiment examined prepulse-pulse time intervals (30–2000 ms). While prepulse inhibition produced by prepulses occurring 60–500 ms before the startle stimulus was disrupted by 10 mg/kg of ketamine, prepulses preceding the startle stimulus by only 30 ms produced either no effect or slight prepulse facilitation under control conditions, and significant prepulse facilitation when ketamine was administered. A fourth experiment examined the time course of prestimulus modification by continuous lead stimuli, ranging in onset from 15 to 75 ms before the startle stimulus. Prepulse facilitation, when observed, tended to occur in earlier portions of the session and was enhanced by ketamine. These results suggest that prestimulus modification of the startle reflex has important parametric and experiential determinants that may influence the effects of drugs. Some of these temporal determinants may have relevance to sensorimotor function in schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244303
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The acoustic startle response as a measure of behavioral dependence in rats (1992)
    Springer
    Psychopharmacology 108 (1992), S. 40-46 
    Details
    ISSN: 1432-2072
    Keywords: Physical dependence ; Acoustic startle response ; Withdrawal ; Morphine ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05–0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in nondependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4–5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3–10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response. These results suggest that the acoustic startle response may be a useful objective measure in evaluating physical dependence produced by substances of abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245283
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    Paper (German National Licenses)
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  • 4
    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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    Paper (German National Licenses)
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