Convergence and Divergence in the Neurochemical Regulation of Prepulse Inhibition of Startle and N40 Suppression in Rats

Swerdlow, Neal R.; Geyer, Mark A.; Shoemaker, Jody M.; Light, Gregory A.; Braff, David L.; Stevens, Karen E.; Sharp, Richard F.; Breier, Michelle R.; Neary, Alaina C.; Auerbach, Pamela P.

doi:10.1038/sj.npp.1300841

Cited by 54 publications

(57 citation statements)

References 55 publications

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“…This supports the suggestion that while PPI and P50 do not share the same neural networks, they may share overlapping networks (Oranje et al, 2006) and hence it is possible that both serotonin and dopamine's modulation of PPI and P50 may be similar within critical areas of the overlapping network. These findings in general support observations in animals with equivalent measures on the neurochemical regulation of sensorimotor and sensory gating (Swerdlow et al, 2006).…”

Section: Combined Serotonin and Dopamine Depletionsupporting

confidence: 87%

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/ phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.

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Section: Combined Serotonin and Dopamine Depletionsupporting

confidence: 87%

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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“…The lack of a correlation between PPI and auditory gating in the paired tone paradigm further corroborates evidence from human and animal studies that these paradigms measure two distinct mechanisms (Brenner et al, 2004;Ellenbroek et al, 1999;Swerdlow et al, 2006).…”

Section: Auditory Gatingsupporting

confidence: 75%

“…So far, most, but not all, studies in rats showed impairments of N40 -gating (the putative rat correlate of the human N100) with NMDAR blocking (Miller et al, 1992;de Bruin et al, 1999;Swerdlow et al, 2006). However, no effect of NMDAR antagonists on auditory gating was observed in a study in mice (Connolly et al, 2004).…”

Section: Auditory Gatingmentioning

confidence: 99%

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Bickel

Lipp

Umbricht

2007

Neuropsychopharmacol

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Cognitive deficits in schizophrenia include impairments at automatic, preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition-(PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N ¼ 15) and their wild-type littermates (N ¼ 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function.

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“…The primary focus of this study was to investigate interactions between 5-HTT genotype, prenatal stress, and postnatal adversity and their interaction on hippocampal glucocorticoid receptor (GR) expression, the HPA stress response, and behaviors, all known to be influenced by early adversity and/or by the 5-HT system, including startle responses, PPI (Borrell, Vela, Arevalo-Martin, Molina-Holgado, & Guaza, 2002;Farid, Martinez, Geyer, & Swerdlow, 2000;Lovic & Fleming, 2004;Swerdlow et al, 2006), and locomotor activity in rats (Burton et al, 2006).…”

mentioning

confidence: 99%

Early adversity and serotonin transporter genotype interact with hippocampal glucocorticoid receptor mRNA expression, corticosterone, and behavior in adult male rats.

Belay

Burton

Lovic

et al. 2011

Behavioral Neuroscience

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Despite its importance for development, relatively little is known about how allelic variation interacts with both pre-and postnatal stress. We examined the interaction between serotonin transporter (5-HTT) genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroid stress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnant dams from gestational Day 10 -21. Postnatal stress involved raising pups after parturition either by their mothers (MR) or in the artificial rearing (AR) paradigm, with or without additional "licking-like" stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, and behaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured in adult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampal GR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioral endpoints tended to be more clearly affected by an interaction between genotype and postnatal environment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatal environment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatal environment to affect behavior. These results are the first to indicate a role for genetic variation in the 5-HTT gene in physiology and behavior in the rat.

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Convergence and Divergence in the Neurochemical Regulation of Prepulse Inhibition of Startle and N40 Suppression in Rats

Cited by 54 publications

References 55 publications

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Early adversity and serotonin transporter genotype interact with hippocampal glucocorticoid receptor mRNA expression, corticosterone, and behavior in adult male rats.

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