Alprazolam-induced EEG spectral power changes in rhesus monkeys: a translational model for the evaluation of the behavioral effects of benzodiazepines

Autor:	Laís F. Berro, James K. Rowlett, John S. Overton, Jaren A. Reeves-Darby
Rok vydání:	2021
Předmět:	Male medicine.drug_class Electromyography Electroencephalography Article Benzodiazepines 03 medical and health sciences 0302 clinical medicine Telemetry medicine Animals Humans Hypnotics and Sedatives Pharmacology Sleep Stages Benzodiazepine Alprazolam medicine.diagnostic_test business.industry GABAA receptor Electrooculography Macaca mulatta 030227 psychiatry Sleep business Neuroscience 030217 neurology & neurosurgery medicine.drug
Zdroj:	Psychopharmacology (Berl)
ISSN:	1432-2072 0033-3158
DOI:	10.1007/s00213-021-05793-z
Popis:	RATIONALE: Benzodiazepines induce electroencephalography (EEG) changes in rodents and humans that are associated with distinct behavioral effects and have been proposed as quantitative biomarkers for GABA(A) receptor modulation. Specifically, central EEG beta and occipital EEG delta activity have been associated with anxiolysis and sedation, respectively. The extent to which nonhuman primates show the same dose- and topography-dependent effects remained unknown. OBJECTIVES: We aimed at establishing a nonhuman primate model for the evaluation of benzodiazepine EEG pharmacology. METHODS: Four adult male rhesus monkeys were prepared with fully implantable telemetry devices that monitored activity, peripheral body temperature, and contained two EEG (central and occipital), one electromyography (EMG) and one electrooculography channel. We investigated daytime alprazolam-induced changes in EEG spectral power, sleep-wake states, EMG activity, locomotor activity and body temperature. Alprazolam (0.01–1.8 mg/kg, i.m.) or vehicle were administered acutely, and telemetry recording was conducted for 1h. RESULTS: Daytime alprazolam dose-dependently increased central EEG power (including beta activity), increased occipital EEG delta power, and decreased occipital EEG alpha, theta and sigma power. There was an ~8-fold difference in the potency of alprazolam to increase central EEG beta vs. occipital EEG delta activity (based on relative EEG power). The highest dose, which increased both central EEG beta and occipital EEG delta relative power, induced sedative effects (increased time spent in N1 and N2 sleep stages) and decreased peripheral body temperature and locomotor activity. CONCLUSIONS: Alprazolam induces dose- and topography-dependent EEG changes in rhesus monkeys, and provides a valuable model for studying benzodiazepine pharmacology.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2cc17c831344227f6ea9be6568cbc02c https://doi.org/10.1007/s00213-021-05793-z Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.