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bioRxiv · 10.1101/2022.04.01.486740

Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments

Castro-Zavala, A.·Alegre-Zurano, L.·Cantacorps, L.·Gallego-Landin, I.·Welz, P.-S.·Aznar Benitah, S.·Valverde, O.
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Abstract

Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Recently, its function has also been associated with alterations in mood, and reward processing. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in mice, as well as how these alterations affect rewarding effects of cocaine. Additionally, key clock genes and components of the dopamine system were assessed in several brain areas. Our results evidence behavioural alterations in Bmal1-KO mice including changes in locomotor activity with impaired habituation to environments as well as short term memory and social recognition impairments. In addition, Bmal1-KO mice experienced reduced cocaine-induced sensitization and rewarding effects of cocaine as well as reduced cocaine-seeking behaviour. Furthermore, Bmal1 deletion influenced the expression of other clock-related genes in the mPFC and striatum as well as alterations in the expression of dopaminergic elements. Overall, the present article offers a novel and extensive characterization of Bmal1-KO animals. We suggest that reduced cocaines rewarding effects in these mutant mice might be related to Bmal1 role as an expression regulator of MAO and TH, two essential enzymes involved in dopamine metabolism.

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Castro-Zavala, A., Alegre-Zurano, L., Cantacorps, L., Gallego-Landin, I., Welz, P.-S., Aznar Benitah, S., Valverde, O.. 2022-04-05. Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments. https://doi.org/10.1101/2022.04.01.486740

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