A preliminary study of the effects of an antimuscarinic agent on anxious behaviors and white matter microarchitecture in nonhuman primates.

Autor: Aggarwal N; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA. naggarwal5@wisc.edu., Oler JA; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA., Tromp DPM; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA., Roseboom PH; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA., Riedel MK; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA., Elam VR; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA., Brotman MA; Neuroscience and Novel Therapeutics Unit, National Institute of Mental Health, Bethesda, MD, 20892, USA., Kalin NH; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53719, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Jan; Vol. 49 (2), pp. 405-413. Date of Electronic Publication: 2023 Jul 29.
DOI: 10.1038/s41386-023-01686-1
Abstrakt: Myelination subserves efficient neuronal communication, and alterations in white matter (WM) microstructure have been implicated in numerous psychiatric disorders, including pathological anxiety. Recent work in rodents suggests that muscarinic antagonists may enhance myelination with behavioral benefits; however, the neural and behavioral effects of muscarinic antagonists have yet to be explored in non-human primates (NHP). Here, as a potentially translatable therapeutic strategy for human pathological anxiety, we present data from a first-in-primate study exploring the effects of the muscarinic receptor antagonist solifenacin on anxious behaviors and WM microstructure. 12 preadolescent rhesus macaques (6 vehicle control, 6 experimental; 8F, 4M) were included in a pre-test/post-test between-group study design. The experimental group received solifenacin succinate for ~60 days. Subjects underwent pre- and post-assessments of: 1) anxious temperament (AT)-related behaviors in the potentially threatening no-eye-contact (NEC) paradigm (30-min); and 2) WM and regional brain metabolism imaging metrics, including diffusion tensor imaging (DTI), quantitative relaxometry (QR), and FDG-PET. In relation to anxiety-related behaviors expressed during the NEC, significant Group (vehicle control vs. solifenacin) by Session (pre vs. post) interactions were found for freezing, cooing, and locomotion. Compared to vehicle controls, solifenacin-treated subjects exhibited effects consistent with reduced anxiety, specifically decreased freezing duration, increased locomotion duration, and increased cooing frequency. Furthermore, the Group-by-Session-by-Sex interaction indicated that these effects occurred predominantly in the males. Exploratory whole-brain voxelwise analyses of post-minus-pre differences in DTI, QR, and FDG-PET metrics revealed some solifenacin-related changes in WM microstructure and brain metabolism. These findings in NHPs support the further investigation of the utility of antimuscarinic agents in targeting WM microstructure as a means to treat pathological anxiety.
(© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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