CRF-receptor1 modulation of the dopamine projection to prelimbic cortex facilitates cognitive flexibility after acute and chronic stress.

Autor:	Mor D; School of Medical Sciences, University of Sydney, Australia., Becchi S; Decision Neuroscience Lab, University of New South Wales, Australia., Bowring J; School of Medical Sciences, University of Sydney, Australia., Tsoukalas M; School of Medical Sciences, University of Sydney, Australia., Balleine BW; Decision Neuroscience Lab, University of New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	Neurobiology of stress [Neurobiol Stress] 2021 Dec 24; Vol. 16, pp. 100424. Date of Electronic Publication: 2021 Dec 24 (Print Publication: 2022).
DOI:	10.1016/j.ynstr.2021.100424
Abstrakt:	Stress reduces cognitive flexibility and dopamine D1 receptor-related activity in the prelimbic cortex (PL), effects hypothesized to depend on reduced corticotropic releasing factor receptor type 1 (CRFr1) regulation of dopamine neurons in the ventral tegmental area (VTA). We assessed this hypothesis in rats by examining the effect of chronic unpredictable restraint stress (CUS), mild acute stress, or their combination on cognitive flexibility, CRFr1 expression in the VTA and D1-related activity in PL. In Experiment 1, rats received either CUS or equivalent handling for 14 days before being trained to press two levers to earn distinct food outcomes. Initial learning was assessed using an outcome devaluation test after which cognitive flexibility was assessed by reversing the outcomes earned by the actions. Prior to each reversal training session, half the CUS and controls receiving acute stress with action-outcome updating assessed using a second devaluation test and CRFr1 expression in the VTA assessed using in-situ hybridisation. Although CUS did not itself affect action-outcome learning, its combination with acute stress blocked reversal learning and decreased VTA CRFr1 expression after acute shock. The relationship between these latter two effects was assessed in Experiment 2 by pharmacologically disconnecting the VTA and PL, unilaterally blocking neurons expressing CRFr1 in the VTA and D1 receptors in the contralateral PL during reversal learning after acute stress. Acute stress again blocked reversal learning but only in the group with VTA-PL disconnection, demonstrating that VTA CRFr1-induced facilitation of dopaminergic activity in the PL is necessary for maintaining cognitive flexibility after acute stress. [250]. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Crown Copyright © 2021 Published by Elsevier Inc.)
Databáze:	MEDLINE
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