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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
de Oliveira, Amanda R. [1, 2] ; Reimer, Adriano E. [2] ; Simandl, Gregory J. [2] ; Nagrale, Sumedh S. [2] ; Widge, Alik S. [2]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Fed Univ Sao Carlos UFSCar, Dept Psychol, Sao Carlos, SP - Brazil
[2] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: TRANSLATIONAL PSYCHIATRY; v. 11, n. 1 MAY 24 2021.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 17/22473-9 - Efeitos da estimulação optogenética córtico-estriatal persistente sobre a flexibilidade comportamental na busca por um modelo animal de Transtorno Obsessivo-Compulsivo (TOC)
Beneficiário:Amanda Ribeiro de Oliveira
Modalidade de apoio: Bolsas no Exterior - Pesquisa