Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons

Swerdlow, Neal R.; Stephany, Nora; Shoemaker, Jody M.; Ross, Laura; Wasserman, Lindsay; Talledo, Jo; Auerbach, Pamela P.

doi:10.1007/s00213-002-1172-5

Cited by 43 publications

(53 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous reports in HS, acute exposure to NMDA antagonists led to greater levels of both PPI (Duncan et al, 2001;Abel et al, 2003;Swerdlow et al, 2002bSwerdlow et al, , 2009 and-in the case of memantine-MMN (Korostenskaja et al, 2007), but the present findings provide the first evidence for such effects in CPD patients. Conceivably, NMDA activity might be deficient within substrates responsible for core CPD symptoms, but be normal or even elevated in other brain regions regulating PPI and MMN.…”

Section: Discussioncontrasting

confidence: 53%

“…Interestingly, whereas NMDA systems have been implicated in the regulation of both PPI and MMN, the evidence linking reduced NMDA activity to deficits in PPI and/or MMN is not entirely straightforward. Thus, PPI is actually increased in healthy subjects (HS) by NMDA antagonists such as ketamine (Duncan et al, 2001;Abel et al, 2003), the low-to moderate-affinity NMDAreceptor antagonist, memantine (Swerdlow et al, 2009), and by the mixed NMDA antagonist/dopamine agonist, amantadine (Swerdlow et al, 2002b). Although MMN has been reported to be reduced in HS by ketamine (Umbricht et al, 2000;Umbricht et al, 2002), it has also been shown to be increased by memantine (Korostenskaja et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n = 84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

show abstract

Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…While NMDA antagonists are generally reported to disrupt PPI in rodents, PPI is actually increased in healthy subjects (HS) by NMDA antagonists such as ketamine (Duncan et al 2001;Abel et al 2003) and by the mixed NMDA antagonist/dopamine agonist, amantadine (Swerdlow et al 2002). In intact rats, we detected PPI-enhancing effects of memantine, using relatively short (10-30 ms) prepulse intervals (Swerdlow et al 2009).…”

Section: Drug-enhanced Ppi As a Biomarker For Pact?mentioning

confidence: 84%

Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

Swerdlow

Light

2015

Translational Neuropsychopharmacology

View full text Add to dashboard Cite

Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct levels for schizophrenia (SZ) therapeutics, neurophysiological endophenotypes, and potential causative insults for this group of disorders. However, with the growing recognition of the heterogeneity of the schizophrenias, and the less sanguine view of the clinical value of antipsychotic (AP) medications, our field must look beyond "validity," to assess the actual utility of these models. At a substantial cost in terms of research support and intellectual capital, what has come from these models, that we can say has actually helped schizophrenia patients? Such introspection is timely, as we are reassessing not only our view of the genetic and pathophysiological diversity of these disorders, but also the predominant strategies for SZ therapeutics; indeed, our field is gaining awareness that we must move away from a "find what's broke and fix it" approach, toward identifying spared neural and cognitive function in SZ patients, and matching these residual neural assets with learning-based therapies. Perhaps, construct-valid models that identify evidence of "spared function" in neural substrates might reveal opportunities for future therapeutics and allow us to study these substrates at a mechanistic level to maximize opportunities for neuroplasticity. Such an effort will require a retooling of our models, and more importantly, a re-evaluation of their utility. For animal models to remain relevant in the search for schizophrenia therapeutics, they will need to focus less on what is valid and focus more on what is useful.

show abstract

“…Alternatively, as reported in animals (Martin-Iverson and Else, 2000;Swerdlow et al, 2001Swerdlow et al, , 2002b and as discussed for the serotonin section, inconsistencies may be related, in part, to differences in PPI stimulus parameters including lead intervals and their sensitivity to dopaminergic modulation. Furthermore, there is increasing evidence that the effects of dopaminergic drugs on PPI may be related to baseline PPI, with greater reductions reported in subjects with high baseline PPI (Bitsios et al, 2005;Giakoumaki et al, 2007).…”

Section: Dopamine Depletionmentioning

confidence: 92%

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

View full text Add to dashboard Cite

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.

show abstract

Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons

Cited by 43 publications

References 62 publications

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

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

Contact Info

Product

Resources

About