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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Lost in translation: no effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats

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Author(s):
de Oliveira, Amanda R. [1, 2] ; Reimer, Adriano E. [2] ; Simandl, Gregory J. [2] ; Nagrale, Sumedh S. [2] ; Widge, Alik S. [2]
Total Authors: 5
Affiliation:
[1] Fed Univ Sao Carlos UFSCar, Dept Psychol, Sao Carlos, SP - Brazil
[2] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 - USA
Total Affiliations: 2
Document type: Journal article
Source: TRANSLATIONAL PSYCHIATRY; v. 11, n. 1 MAY 24 2021.
Web of Science Citations: 0
Abstract

The orbitofrontal cortex-ventromedial striatum (OFC-VMS) circuitry is widely believed to drive compulsive behavior. Hyperactivating this pathway in inbred mice produces excessive and persistent self-grooming, which has been considered a model for human compulsivity. We aimed to replicate these findings in outbred rats, where there are few reliable compulsivity models. Male Long-Evans rats implanted with optical fibers into VMS and with opsins delivered into OFC received optical stimulation at parameters that produce OFC-VMS plasticity and compulsive grooming in mice. We then evaluated rats for compulsive self-grooming at six timepoints: before, during, immediately after, and 1h after each stimulation, 1 and 2 weeks after the ending of a 6-day stimulation protocol. To further test for effects of OFC-VMS hyperstimulation, we ran animals in three standard compulsivity assays: marble burying, nestlet shredding, and operant attentional set-shifting. OFC-VMS stimulation did not increase self-grooming or induce significant changes in nestlet shredding, marble burying, or set-shifting in rats. Follow-on evoked potential studies verified that the stimulation protocol altered OFC-VMS synaptic weighting. In sum, although we induced physiological changes in the OFC-VMS circuitry, we could not reproduce in a strongly powered study in rats a model of compulsive behavior previously reported in mice. This suggests possible limitations to translation of mouse findings to species higher on the phylogenetic chain. (AU)

FAPESP's process: 17/22473-9 - Effects of persistent cortico-striatal optogenetic stimulation on behavioral flexibility in the search for an animal model of Obsessive-Compulsive Disorder (OCD)
Grantee:Amanda Ribeiro de Oliveira
Support Opportunities: Scholarships abroad - Research