Test-retest reliability of tone- and 40 Hz train-evoked gamma oscillations in female rats and their sensitivity to low-dose NMDA channel blockade.
Psychopharmacology (Berl)
; 238(8): 2325-2334, 2021 Aug.
Article
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| MEDLINE
| ID: mdl-33944972
ABSTRACT
RATIONALE Schizophrenia patients consistently show deficits in sensory-evoked broadband gamma oscillations and click-evoked entrainment at 40 Hz, called the 40-Hz auditory steady-state response (ASSR). Since such evoked oscillations depend on cortical N-methyl D-aspartic acid (NMDA)-mediated network activity, they can serve as pharmacodynamic biomarkers in the preclinical and clinical development of drug candidates engaging these circuits. However, there are few test-retest reliability data in preclinical species, a prerequisite for within-subject testing paradigms. OBJECTIVE:
We investigated the long-term psychometric stability of these measures in a rodent model.METHODS:
Female rats with chronic epidural implants were used to record tone- and 40 Hz click-evoked responses at multiple time points and across six sessions, spread over 3 weeks. We assessed reliability using intraclass correlation coefficients (ICC). Separately, we used mixed-effects ANOVA to examine time and session effects. Individual subject variability was determined using the coefficient of variation (CV). Lastly, to illustrate the importance of long-term measure stability for within-subject testing design, we used low to moderate doses of an NMDA antagonist MK801 (0.025-0.15 mg/kg) to disrupt the evoked response.RESULTS:
We found that 40-Hz ASSR showed good reliability (ICC=0.60-0.75), while the reliability of tone-evoked gamma ranged from poor to good (0.33-0.67). We noted time but no session effects. Subjects showed a lower variance for ASSR over tone-evoked gamma. Both measures were dose-dependently attenuated by NMDA antagonism.CONCLUSION:
Overall, while both evoked gamma measures use NMDA transmission, 40-Hz ASSR showed superior psychometric properties of higher ICC and lower CV, relative to tone-evoked gamma.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Receptores de N-Metil-D-Aspartato
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Antagonistas de Aminoácidos Excitadores
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Ritmo Gamma
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2021
Tipo del documento:
Article