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

Autor(es)

de Oliveira, Amanda R. ^{[1, 2]} ; Reimer, Adriano E. ^[2] ; Simandl, Gregory J. ^[2] ; Nagrale, Sumedh S. ^[2] ; Widge, Alik S. ^[2]

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

• 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