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  • 1
    Electronic Resource
    Electronic Resource
    Disruption of prepulse inhibition in mice lacking mGluR1 (2003)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 18 (2003), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sensorimotor gating, measured by prepulse inhibition of the startle response (PPI), is a cross-species form of information processing that is deficient in patients with schizophrenia and is widely used as a model to study the neurobiology of this disorder. The eight known metabotropic glutamate receptors (mGluRs) are divided into three groups on the basis of sequence homology and pharmacological properties. Group I consists of mGluR5 and mGluR1, both of which are coupled positively to phospholipase C. Mice lacking mGluR5 exhibit a deficit in PPI. Like mGluR5, mGluR1 is located in regions that are involved in the modulation of PPI. To test the hypothesis that mGluR1 is involved in the modulation of PPI we assessed PPI in mGluR1 knockout (KO) mice. Littermate mGluR1 wild-type and KO mice were tested at multiple ages in a standard PPI paradigm containing a 65 dB background, 120 dB pulses and prepulses of 69, 73 and 77 dB. At all ages tested, mGluR1 KO mice exhibited a significant PPI deficit. The PPI deficit of the mGluR1 KO mice was not further exaggerated by administration of the N-methyl-d-aspartate antagonist phencyclidine nor was it reversed by administration of the dopamine antagonist raclopride (3.0 mg/kg). The PPI deficit of the mGluR1 KO mice was, however, ameliorated by administration of the mood stabilizer lamotrigine (27 mg/kg base equivalent weight), though increases in PPI were also seen with lamotrigine in the wild-type mice. Thus, both group I metabotropic glutamate receptors are involved in the regulation of PPI in mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2003.03073.x
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  • 2
    Electronic Resource
    Electronic Resource
    Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats (1998)
    Springer
    Psychopharmacology 135 (1998), S. 296-304 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prepulse inhibition ; Sensorimotor gating ; Sensitization ; Locomotor activity ; Amphetamine ; Apomorphine ; Schizophrenia ; Startle ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed whether repeated injections of d-amphetamine or apomorphine could induce sensitization to the disruptive effects of these psychomotor stimulants on sensorimotor gating in rats. In the first experiment, rats were given six pre-exposures to either 2.0 mg/kg d-amphetamine or saline before being tested for the effects of d-amphetamine (0.0, 0.5, 1.0, 2.0 or 4.0 mg/kg, IP) on prepulse inhibition of acoustic startle (PPI) and locomotor activity. The tests for PPI confirmed that sensorimotor gating could be disrupted by a high dose of d-amphetamine (4.0 mg/kg). However, comparison of the dose-response curves for the drug and saline pre-exposed groups did not reveal evidence for sensitization to this d-amphetamine effect in drug-pre-exposed rats, despite indications that sensitization had developed to the locomotor stimulant effects of d-amphetamine. A similar pattern of results was obtained in a second experiment that examined the effects of apomorphine (0.0, 0.1, 0.2, 0.4 and 0.8 mg/kg, SC) on PPI and locomotion in rats pre-exposed to 2.0 mg/kg of this drug or its vehicle. These findings demonstrate that treatments which induce sensitization to the behavioral activating effects of psychomotor stimulants do not necessarily produce sensitization to the disruptive effects of stimulants on sensorimotor gating. The implications of these results for hypotheses linking sensitization-like processes to the etiology of schizophrenia are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050513
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  • 3
    Electronic Resource
    Electronic Resource
    Sex differences in sensorimotor gating of the human startle reflex: all smoke? (1999)
    Springer
    Psychopharmacology 146 (1999), S. 228-232 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Prepulse inhibition ; Schizophrenia ; Sensorimotor gating ; Startle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: A recent report described sex differences in the effects of nicotine use and withdrawal on prepulse inhibition of acoustic startle (PPI), but no sex differences in PPI in non-smokers. Objective: To determine whether previously reported male〉female acoustic PPI reflect sex differences in smoking effects on PPI, rather than simple sex differences in the regulation of PPI. A retrospective analyses of 〉600 carefully screened normals tested over the past 12 years was completed. Results: Male〉female acoustic PPI was detected in analyses that included: 1) all subjects; or 2) self-declared non-smokers. Conclusions: Sex differences in PPI cannot be accounted for by smoking history, because they are present across a large sample of non-smoking normal controls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051111
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  • 4
    Electronic Resource
    Electronic Resource
    Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild-type and serotonin1B knockout mice (1997)
    Springer
    Psychopharmacology 132 (1997), S. 125-134 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prepulse inhibition ; Habituation ; Sensorimotor gating ; Schizophrenia ; Serotonin 1B receptor ; RU24969 ; 8-OH-DPAT ; Mice ; Startle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two operational measures of central information processing mechanisms are habituation and prepulse inhibition (PPI) of the startle response. Both measures can be assessed reliably in humans and other animals, and have been shown to be deficient in patients with schizophrenia. The three present experiments assessed the involvement of the serotonin1B (5-HT1B) receptor in modulating startle reactivity, habituation, and PPI by comparing 5-HT1B receptor gene knockout (5-HT1B knockout) with wild-type 129/Sv mice. In experiment 1, female mice received saline, 2.0 mg/kg 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), a 5-HT1A/1B agonist, and 1.0 mg/kg 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist. Female mice received saline, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 2, and male mice received saline, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 3. All three studies used identical within-subjects designs. Two phenotypic differences were observed following saline treatment: 5-HT1B knockout mice consistently exhibited a small increase in PPI that achieved significance in experiment 1; and 5-HT1B knockout male mice exhibited robust decreases in startle reactivity. Habituation was disrupted consistently by RU24969 in wild-type but not in 5-HT1B knockout mice, while 8-OH-DPAT had no effect on habituation. Consistent with the phenotypic difference in PPI, the high dose of RU24969 significantly and consistently reduced PPI in wild-type but not in 5-HT1B knockout mice. 8-OH-DPAT increased PPI in both wild-type and 5-HT1B knockout mice in every experiment. These findings suggest that 5-HT1B receptors modulate startle reactivity, habituation, and PPI in mice. Additionally, a potential species difference may exist in the behavioral effects of 5-HT1A receptor activation on PPI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050328
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  • 5
    Electronic Resource
    Electronic Resource
    Serotonin releasers increase prepulse inhibition in serotonin 1B knockout mice (2000)
    Springer
    Psychopharmacology 149 (2000), S. 306-312 
    Details
    ISSN: 1432-2072
    Keywords: Key words Startle ; Sensorimotor gating ; Serotonin 1B receptor ; MBDB ; MDMA ; GR 127935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition (PPI) is the normal reduction of the startle response which occurs when an abrupt startling stimulus is preceded by a weak pre-stimulus and is decreased in several neuropsychiatric disorders. Objective: The role of the serotonin 1B (5-HT1B) receptor in modulating PPI was investigated using 5-HT-releasing agents in wild-type (WT) and 5-HT1B knockout (1BKO) mice. Whether the differential effects of 5-HT-releasing agents on PPI in WT and 1BKO mice resulted from lack of the 5-HT1B receptor or altered development was also assessed. Methods: PPI was assessed in WT and 1BKO mice treated with the 5-HT-releasing agents (+)3,4-methylenedioxy-N-methylamphetamine (MDMA: 0, 10 mg/kg) or (±)N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB: 0, 10 mg/kg). Additionally, intact 129 Sv mice received pre-treatments of the 5-HT1B/1D antagonist GR 127935 (0, 0.75, 1.5, 3.0 mg/kg) and treatments of MDMA (10 mg/kg). Results: MDMA and MBDB increased PPI in 1BKO mice, but did not alter PPI in WT mice. Intact 129 Sv mice receiving 3.0 mg/kg GR 127935 and 10 mg/kg MDMA exhibited increases in PPI. Conclusions: The ability of GR 127935 to increase PPI in intact MDMA-treated mice suggests that lack of the 5-HT1B receptor, and not altered development, is responsible for the PPI-increasing effects of 5-HT releasers in 1BKO mice. 5-HT release activates multiple 5-HT receptor subtypes, which individually may increase or decrease PPI and together have a combined effect on PPI. Our finding that MDMA and MBDB increase PPI in 1BKO, but not WT mice, indicates that the activation of 5-HT1B receptors by 5-HT disrupts PPI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000373
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  • 6
    Electronic Resource
    Electronic Resource
    Presynaptic dopamine-glutamate interactions in the nucleus accumbens regulate sensorimotor gating (1995)
    Springer
    Psychopharmacology 120 (1995), S. 433-441 
    Details
    ISSN: 1432-2072
    Keywords: Accumbens ; Dopamine ; Glutamate ; Prepulse ; Schizophrenia ; Sensorimotor ; Startle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) is the normal reduction in startle reflex that occurs when a startling stimulus is preceded by a weak prepulse. PPI is reduced in patients with schizophrenia and in rats after central dopamine (DA) activation. The DA agonist-induced disruption of PPI in rats may thus model some features of impaired sensorimotor gating in schizophrenia. Ascending DAergic and descending glutamatergic fibers converge within the nucleus accumbens (NAC), and interactions at this DA-glutamate interface have been implicated in the pathophysiology of schizophrenia. In this study, we examined the role of NAC DA-glutamate interactions in the regulation of PPI in rats. Intra-NAC infusion of the non-NMDA antagonist, CNQX, attenuated the PPI-disruptive effects ofd-amphetamine (AMPH), but CNQX did not affect PPI when injected alone, nor did it reverse the PPI-disruptive effects of the direct D2/D3 agonist quinpirole. Intra-NAC infusion of the non-NMDA agonist AMPA significantly reduced PPI. The PPI-disruptive effects of AMPA were blocked by haloperidol and by 6-hydroxydopamine (6OHDA) lesions of the NAC. These data suggest that the PPI-disruptive effects of AMPH are dependent on tonic non-NMDA receptor activation in the NAC, and that non-NMDA receptor activation in the NAC results in a DA-dependent reduction in PPI. The parsimonious interpretation of these data is that non-NMDA glutamate receptors in the NAC facilitate presynaptic DA function, and that this DA-glutamate interaction is a critical regulatory substrate of sensorimotor gating.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245815
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  • 7
    Electronic Resource
    Electronic Resource
    Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine (1995)
    Springer
    Psychopharmacology 122 (1995), S. 35-43 
    Details
    ISSN: 1432-2072
    Keywords: Prepulse inhibition of startle ; Sensorimotor gating ; Neonatal lesion ; Hippocampus ; Ibotenic acid ; Apomorphine ; Startle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal excitotoxic hippocampal damage in the rat results in postpubertal onset of a variety of abnormal behaviors related to excessive dopaminergic transmission in the mesolimbic/nigrostriatal system, and thus may be considered an animal model of some aspects of schizophrenia. Because sensorimotor gating is impaired in adult patients with schizophrenia and in rats with experimentally induced mesolimbic dopamine hyperactivity, the present experiments investigated the effects of neonatal (postnatal day 7, PD7) ibotenic acid (3 µg) lesions of the ventral hippocampus (VH) on the amplitude and prepulse inhibition (PPI) of acoustic startle in prepubertal (PD35) and postpubertal (PD56) rats. Startle was elicited using 105 and 118-dB pulses alone or preceded by 4, 8, or 16 dB above-background prepulses in rats treated with vehicle or apomorphine (APO; 0.025 or 0.1 mg/kg SC). At PD35, PPI in VH-lesioned rats did not differ significantly from these measures in sham operated rats. Apomorphine significantly increased startle amplitude and reduced PPI in both sham operated and VH-lesioned rats at PD35. At PD56, startle amplitude in VH-lesioned rats was not significantly different from controls, but PPI was reduced significantly compared to controls. Ventral hippocampus lesioned rats also exhibited an exaggerated reduction in PPI after treatment with APO. These findings provide further evidence of postpubertal impairments that may be related to increased mesolimbic dopamine transmission and receptor sensitivity in rats with neonatal hippocampal damage, and provide further support for the fidelity of this animal model of schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246439
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence for a functional interaction between 5-HT1A and 5-HT2 receptors in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 69-74 
    Details
    ISSN: 1432-2072
    Keywords: Key words 8-OH-DPAT ; DOI ; Isobologram ; 5-HT1A/2 interaction ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Evidence of a functional interaction between serotonin 5-HT1A and 5-HT2 receptor subtypes has been compromised by incomplete experimental designs and conflicting data. To test for such an interaction, combinations of the 5-HT1A agonist 8-OH-DPAT and the 5-HT2 agonist DOI were administered to rats prior to testing of locomotor activity in the Behavioral Pattern Monitor (BPM). The BPM is an activity and holeboard chamber that enables analyses of quantitative and qualitative changes in locomotor and investigatory activity. Dose-response studies of 8-OH-DPAT and DOI alone and in the presence of selected doses of the other drug were performed in order to allow isobolographic analysis, which characterizes the relationship of two drugs as either additive (no interaction), supra-additive, or infra-additive. Rats treated with saline, 8-OH-DPAT (6.25, 12.5, 25, or 50 μg/kg SC), DOI (0.15, 0.3, or 0.6 mg/kg SC), or selected combinations of both drugs were tested in the BPM for 1 h. Isobolographic analysis of the effects on locomotor activity revealed that 8-OH-DPAT and DOI interact in an infra-additive manner. Thus, at a functional level, 5-HT1A and 5-HT2 receptors interact antagonistically in the modulation of locomotor activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050740
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  • 9
    Electronic Resource
    Electronic Resource
    Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens (1990)
    Springer
    Psychopharmacology 101 (1990), S. 414-420 
    Details
    ISSN: 1432-2072
    Keywords: Acoustic startle response ; Dopamine ; Nucleus accumbens ; Prepulse inhibition ; Schizophrenia ; Sensorimotor gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that several dopamine agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. Schizophrenic patients also exhibit deficits in PPI when the prepulse preceeds the startle stimulus by less than 500 ms. In experiment 1, dopamine (0–40 µg) infused directly into the nucleus accumbens in rats caused a dose-dependent decrease in PPI at prepulse intervals shorter than 500 ms. In experiment 2, this effect of accumbens dopamine infusions on sensorimotor gating was found to vary with changes in prepulse intensity. These findings strongly suggest that increased mesolimbic dopamine activity is one substrate of the sensorimotor gating deficits in rats that are caused by treatment with dopamine agonists; similar substrates might mediate deficits in PPI exhibited by schizophrenic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244063
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  • 10
    Electronic Resource
    Electronic Resource
    Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of startle in the rat (1991)
    Springer
    Psychopharmacology 105 (1991), S. 347-354 
    Details
    ISSN: 1432-2072
    Keywords: Prepulse inhibition ; Sensorimotor gating ; Startle ; Hippocampus ; Dopamine ; Schizophrenia ; Carbachol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) is the decrease in a startle response that occurs when the startling stimulus is preceded by a weaker stimulus or “prepulse”. Schizophrenic patients exhibit abnormally low levels of PPI when the prepulse precedes the startle stimulus by less than 500 ms. A similar deficit in sensorimotor gating can be demonstrated in rats after stimulation of D2 dopamine (DA) receptors by systemic administration of DA agonists or by infusion of DA directly into the nucleus accumbens. We now demonstrate that carbachol infusion into the dentate gyrus of the hippocampal formation disrupts PPI in the rat. This disruption of sensorimotor gating occurs when the startling stimulus is either acoustic or tactile. Carbachol infusion into the neocortex has no effect on PPI. While pretreatment with the D2 DA receptor antagonist spiperone reverses the disruption of PPI caused by systemic administration of apomorphine, this pretreatment fails to reverse the disruption of PPI induced by carbachol infusion into the hippocampus. These results demonstrate that pharmacologic stimulation of the hippocampus disrupts sensorimotor gating in the rat by a mechanism distinct from that of DA agonists. Prepulse inhibition of the startle reflex is an animal model in which pharmacologic stimulation of the hippocampus mimics the deficits in sensorimotor gating observed in schizophrenic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244429
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