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bioRxiv · 10.1101/2024.10.08.617254

Noradrenergic and Pavlovian underpinnings of compulsive versus adaptive coping strategies

Abstract

BackgroundLoss of control over coping strategies can result in the development of impulsive/compulsive spectrum disorders (ICSDs) such as obsessive-compulsive disorder or trichotillomania. Rats, like humans, show individual differences in their tendency to engage in and maintain control over coping behaviours. While most rats exposed to a schedule-induced polydipsia (SIP) procedure develop controlled, moderate, polydipsic coping, some vulnerable individuals engage in excessive, compulsive drinking, or hyperdipsia. The development of hyperdipsia depends in part on noradrenergic mechanisms, as it is prevented by the noradrenaline reuptake inhibitor, atomoxetine in highly impulsive vulnerable rats. However, whether noradrenergic mechanisms also underlie the expression of well-established hyperdipsia, or if other traits, such as the ICSD-relevant sign-tracking, confer vulnerability to its development, are unknown. MethodsIn two longitudinal studies in male Sprague-Dawley rats, we investigated whether well-established hyperdipsia is influenced by atomoxetine and whether its development is predicted by sign-tracking. ResultsSign-tracking was associated with faster acquisition of SIP and the development of high or compulsive levels of SIP. Chronic atomoxetine both exacerbated hyperdipsia and increased the mRNA levels of the markers of cellular activity and plasticity c-fos and zif268, across the dorsal striatum, as revealed by qPCR assays. Atomoxetine also altered the transcriptomic landscape of the nucleus accumbens shell and the pattern of cFos and zif268 expression in the amygdalo-striatal system. ConclusionsThese results provide new insight into the biobehavioural basis of compulsive behaviours, revealing a differential noradrenergic control of the development and expression of compulsive coping, the latter involving recruitment of distinct striatal processes.

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BibTeXRIS

Chernoff, C. S., Belin-Rauscent, A., Puaud, M., Torrisi, S. A., Fouyssac, M. S., Nemeth, B., Yu, C., Higuera-Matas, A., Jones, S., Belin, D.. 2024-10-12. Noradrenergic and Pavlovian underpinnings of compulsive versus adaptive coping strategies. https://doi.org/10.1101/2024.10.08.617254

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